Pub Date : 2023-01-01DOI: 10.2174/1567205020666230614143027
Khaled M Khleifat, Nafe M Al-Tawarah, Mohammad A Al-Kafaween, We'am Al-Ksasbeh, Haitham Qaralleh, Moath Alqaraleh, Khawla D Al-Hamaideh, Yousef M Al-Saraireh, Ahmad Z Al-Sarayreh, Yaseen T Al-Qaisi, Abu Bakar Mohd Hilmi
Background/objective: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD.
Methods: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively.
Results: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner.
Conclusion: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.
{"title":"Memory Enhancing and Neurogenesis Activity of Honey Bee Venom in the Symptoms of Amnesia: Using Rats with Amnesia-like Alzheimer's Disease as a Model.","authors":"Khaled M Khleifat, Nafe M Al-Tawarah, Mohammad A Al-Kafaween, We'am Al-Ksasbeh, Haitham Qaralleh, Moath Alqaraleh, Khawla D Al-Hamaideh, Yousef M Al-Saraireh, Ahmad Z Al-Sarayreh, Yaseen T Al-Qaisi, Abu Bakar Mohd Hilmi","doi":"10.2174/1567205020666230614143027","DOIUrl":"https://doi.org/10.2174/1567205020666230614143027","url":null,"abstract":"<p><strong>Background/objective: </strong>Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD.</p><p><strong>Methods: </strong>The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively.</p><p><strong>Results: </strong>During the nootropic phase, treatment groups demonstrated a significant (<i>P</i> < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (<i>P</i> < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (<i>P</i> < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (<i>P</i> < 0.05) in a dose-dependent manner.</p><p><strong>Conclusion: </strong>This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"20 3","pages":"190-201"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10227185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-10DOI: 10.2174/1567205019666220610155608
R. Khandia, Neerja Viswanathan, Shailja Singhal, T. Alqahtani, Mohannad A Almikhlafi, Alexander Nikolaevich Simonov, Ghulam Md Ashraf
INTRODUCTION Alzheimer's Disease (AD) is a progressive, neurodegenerative disease that severely affects affected individuals' cognitive abilities, memory, and quality of life. It affects the elderly population, and there is no permanent prevention or cures available today, treatments mainly aiming to alleviate the symptoms as and when they appear. Alternate therapeutic approaches are being researched constantly, and there is a growing focus on phytomedicine, herbal medicine, organic compounds, ayurvedic compounds for the treatment of AD. METHODS The current study aims to provide an extensive review of these plants against AD from the currently existing literature. Most relevant keywords like Alzheimer's Disease, phytomedicines, ethnic medicines, the role of phytomedicine in neuroprotection, common phytomedicines against AD etc., were used to select the plants and their metabolites effective in treating AD. The study focuses on six plants: Panax ginseng, Ginkgo biloba, Bacopa monnieri, Withania somnifera, Curcuma longa, and Lavandula angustifolia. Their active components have been studied alongwith, neuroprotective properties, and evidence of in-vitro, pre-clinical studies, and clinical studies conducted to prove their therapeutic potential against the disease have been presented. RESULTS All plants envisaged in the study show potential for fighting against AD to varying degrees. Their compounds have shown therapeutic effect by reversing the neurological changes such as clearing Aβ plaque and neurofibrillary tangle formation, and ameliorative effects against neurodegeneration through processes including improving concentration, memory, cognition and learning, higher working and cue memory, improved spatial memory, inhibition of NF-κB expression, inhibiting the release of pro-inflammatory cytokines, inhibition of AChE and lipid peroxidase enzymes, and reduction of interleukin levels and tumor necrosis factor-alpha. CONCLUSION The present review is a comprehensive and up-to-date analysis supported with the evidentiary profs from pre-clinical studies, meta-analyses, and review papers related to natural phytochemicals' impact on neurodegenerative disorders like AD.
{"title":"Ameliorative effects of phytomedicines on Alzheimer's patients.","authors":"R. Khandia, Neerja Viswanathan, Shailja Singhal, T. Alqahtani, Mohannad A Almikhlafi, Alexander Nikolaevich Simonov, Ghulam Md Ashraf","doi":"10.2174/1567205019666220610155608","DOIUrl":"https://doi.org/10.2174/1567205019666220610155608","url":null,"abstract":"INTRODUCTION\u0000Alzheimer's Disease (AD) is a progressive, neurodegenerative disease that severely affects affected individuals' cognitive abilities, memory, and quality of life. It affects the elderly population, and there is no permanent prevention or cures available today, treatments mainly aiming to alleviate the symptoms as and when they appear. Alternate therapeutic approaches are being researched constantly, and there is a growing focus on phytomedicine, herbal medicine, organic compounds, ayurvedic compounds for the treatment of AD.\u0000\u0000\u0000METHODS\u0000The current study aims to provide an extensive review of these plants against AD from the currently existing literature. Most relevant keywords like Alzheimer's Disease, phytomedicines, ethnic medicines, the role of phytomedicine in neuroprotection, common phytomedicines against AD etc., were used to select the plants and their metabolites effective in treating AD. The study focuses on six plants: Panax ginseng, Ginkgo biloba, Bacopa monnieri, Withania somnifera, Curcuma longa, and Lavandula angustifolia. Their active components have been studied alongwith, neuroprotective properties, and evidence of in-vitro, pre-clinical studies, and clinical studies conducted to prove their therapeutic potential against the disease have been presented.\u0000\u0000\u0000RESULTS\u0000All plants envisaged in the study show potential for fighting against AD to varying degrees. Their compounds have shown therapeutic effect by reversing the neurological changes such as clearing Aβ plaque and neurofibrillary tangle formation, and ameliorative effects against neurodegeneration through processes including improving concentration, memory, cognition and learning, higher working and cue memory, improved spatial memory, inhibition of NF-κB expression, inhibiting the release of pro-inflammatory cytokines, inhibition of AChE and lipid peroxidase enzymes, and reduction of interleukin levels and tumor necrosis factor-alpha.\u0000\u0000\u0000CONCLUSION\u0000The present review is a comprehensive and up-to-date analysis supported with the evidentiary profs from pre-clinical studies, meta-analyses, and review papers related to natural phytochemicals' impact on neurodegenerative disorders like AD.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49656688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-14DOI: 10.2174/1567205019666220514131015
Shadi Zarei, G. Lakhanpal, J. Sadavoy
BACKGROUND Caring for a family member with dementia is stressful and challenging. Family caregivers, as a vulnerable marginalized population and invisible backbone of the health care system, need accessible and effective interventions that are tailored to their particular needs. OBJECTIVES To evaluate the feasibility and effectiveness of a live online mindfulness-based cognitive therapy (tele-MBCT) intervention for family caregivers of individuals with dementia. METHOD Family caregivers were assigned to a tele-MBCT intervention or a usual care control group. Tele-MBCT participants attended eight weekly live online training and practiced mindfulness practices at home. All participants completed surveys at baseline, post-intervention, and 4-week follow-up. RESULTS 26 participants (age 60±13 years) were enrolled and randomized (14 into the intervention and 12 into the control group), and 92.3% completed the study. 88% of the participants were female, and 70% were caring for a parent for the mean of 5.12±2.88 years. 84% of the participants in the intervention group attended at least seven sessions and the average of daily practice was 23.58±45.71 minutes. All participants were satisfied with the intervention, and 88.8% were satisfied with the online delivery method. Participants in the intervention group showed Pre-Post improvement in self-compassion (t (11) = -2.49, p=0.03) and coping strategies (t (11) = 3.62, p=0.004) compared to the control group. CONCLUSION Tele-MBCT is a feasible intervention and may improve psychological outcomes and adaptive coping in family caregivers of individuals with dementia. A larger controlled trial is warranted.
{"title":"Tele-Mindfulness for Dementia's Family Caregivers: a Randomized Trial with a Usual Care Control Group.","authors":"Shadi Zarei, G. Lakhanpal, J. Sadavoy","doi":"10.2174/1567205019666220514131015","DOIUrl":"https://doi.org/10.2174/1567205019666220514131015","url":null,"abstract":"BACKGROUND\u0000Caring for a family member with dementia is stressful and challenging. Family caregivers, as a vulnerable marginalized population and invisible backbone of the health care system, need accessible and effective interventions that are tailored to their particular needs.\u0000\u0000\u0000OBJECTIVES\u0000To evaluate the feasibility and effectiveness of a live online mindfulness-based cognitive therapy (tele-MBCT) intervention for family caregivers of individuals with dementia.\u0000\u0000\u0000METHOD\u0000Family caregivers were assigned to a tele-MBCT intervention or a usual care control group. Tele-MBCT participants attended eight weekly live online training and practiced mindfulness practices at home. All participants completed surveys at baseline, post-intervention, and 4-week follow-up.\u0000\u0000\u0000RESULTS\u000026 participants (age 60±13 years) were enrolled and randomized (14 into the intervention and 12 into the control group), and 92.3% completed the study. 88% of the participants were female, and 70% were caring for a parent for the mean of 5.12±2.88 years. 84% of the participants in the intervention group attended at least seven sessions and the average of daily practice was 23.58±45.71 minutes. All participants were satisfied with the intervention, and 88.8% were satisfied with the online delivery method. Participants in the intervention group showed Pre-Post improvement in self-compassion (t (11) = -2.49, p=0.03) and coping strategies (t (11) = 3.62, p=0.004) compared to the control group.\u0000\u0000\u0000CONCLUSION\u0000Tele-MBCT is a feasible intervention and may improve psychological outcomes and adaptive coping in family caregivers of individuals with dementia. A larger controlled trial is warranted.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45865942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-11DOI: 10.2174/1567205019666220511140955
M. Abdul Aziz, Ghulam Md Ashraf, M. Safiqul Islam
BACKGROUND Alzheimer's disease (AD) is the most common form of neurodegenerative disorder. The association of BIN1, CLU and IDE genetic polymorphisms with AD risk have been evaluated overtimes that produced conflicting outcomes. OBJECTIVE We performed this meta-analysis to investigate the contribution of BIN1 (rs744373 and rs7561528), CLU (rs11136000 and rs9331888), and IDE (rs1887922) polymorphisms to AD risk. METHODS From a systemic literature search up to July 15, 2021, we included 25 studies with rs744373, 16 studies with rs7561528, 37 studies with rs11136000, 16 studies with rs9331888, and 4 studies with rs1887922. To analyze the correlation, we constructed seven genetic models that used odds ratio and 95% confidence intervals. We used RevMan 5.4 for meta-analysis. RESULTS Our study suggests that BIN1 rs744373 is associated with a significantly increased risk of AD in five genetic models (OR>1). Again, CLU rs11136000 showed reduced association in all genetic models (OR<1). CLU rs9331888 revealed an increased association in two models (OR>1). The IDE rs1887922 showed significantly increased risk in four models (OR>1). From subgroup analysis, a significantly increased risk of AD was observed in Caucasians and Asians for BIN1 rs744373. Again, BIN1 rs7561528 showed a significantly enhanced risk of AD only in Caucasians. CLU rs11136000 showed significantly reduced risk in Caucasians but rs9331888 showed increased risk in the same ethnicity. CONCLUSION Our meta-analysis confirms the association of BIN1 rs744373, CLU rs9331888 and IDE rs1887922 polymorphisms with an increased risk of AD, especially in Caucasians. Again, CLU rs11136000 is associated with reduced AD risk in the overall population and Caucasians.
{"title":"Link of BIN1, CLU and IDE gene polymorphisms with the susceptibility of Alzheimer's disease: evidence from a meta-analysis.","authors":"M. Abdul Aziz, Ghulam Md Ashraf, M. Safiqul Islam","doi":"10.2174/1567205019666220511140955","DOIUrl":"https://doi.org/10.2174/1567205019666220511140955","url":null,"abstract":"BACKGROUND\u0000Alzheimer's disease (AD) is the most common form of neurodegenerative disorder. The association of BIN1, CLU and IDE genetic polymorphisms with AD risk have been evaluated overtimes that produced conflicting outcomes.\u0000\u0000\u0000OBJECTIVE\u0000We performed this meta-analysis to investigate the contribution of BIN1 (rs744373 and rs7561528), CLU (rs11136000 and rs9331888), and IDE (rs1887922) polymorphisms to AD risk.\u0000\u0000\u0000METHODS\u0000From a systemic literature search up to July 15, 2021, we included 25 studies with rs744373, 16 studies with rs7561528, 37 studies with rs11136000, 16 studies with rs9331888, and 4 studies with rs1887922. To analyze the correlation, we constructed seven genetic models that used odds ratio and 95% confidence intervals. We used RevMan 5.4 for meta-analysis.\u0000\u0000\u0000RESULTS\u0000Our study suggests that BIN1 rs744373 is associated with a significantly increased risk of AD in five genetic models (OR>1). Again, CLU rs11136000 showed reduced association in all genetic models (OR<1). CLU rs9331888 revealed an increased association in two models (OR>1). The IDE rs1887922 showed significantly increased risk in four models (OR>1). From subgroup analysis, a significantly increased risk of AD was observed in Caucasians and Asians for BIN1 rs744373. Again, BIN1 rs7561528 showed a significantly enhanced risk of AD only in Caucasians. CLU rs11136000 showed significantly reduced risk in Caucasians but rs9331888 showed increased risk in the same ethnicity.\u0000\u0000\u0000CONCLUSION\u0000Our meta-analysis confirms the association of BIN1 rs744373, CLU rs9331888 and IDE rs1887922 polymorphisms with an increased risk of AD, especially in Caucasians. Again, CLU rs11136000 is associated with reduced AD risk in the overall population and Caucasians.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48695539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-09DOI: 10.2174/1567205019666220509143823
A. Di Meco, Shahrnaz Kemal, J. Popović, S. Chandra, Katherine R. Sadleir, R. Vassar
BACKGROUND Alzheimer's disease (AD) is initiated by aberrant accumulation of amyloid beta (Aβ) protein in the brain parenchyma. The microenvironment surrounding amyloid plaques is characterized by the swelling of presynaptic terminals (dystrophic neurites) associated with lysosomal dysfunction, microtubule disruption and impaired axonal transport. Aβ-induced plasma membrane damage and calcium influx could be potential mechanisms underlying dystrophic neurite formation. OBJECTIVE We tested whether promoting membrane integrity by brain administration of a safe FDA approved surfactant molecule poloxamer-188 (P188) could attenuate AD pathology in vivo. METHODS Three-month-old 5XFAD male mice were administered several concentrations of P188 in the brain for 42 days with mini-osmotic pumps. After 42 days, mice were euthanized and assessed for amyloid pathology, dystrophic neurites, pathogenic microglia activation, tau phosphorylation and lysosomal / vesicular trafficking markers in the brain. RESULTS P188 was lethal at the highest concentration of 10mM. Lower concentrations of P188 (1.2, 12 and 120μM) were well tolerated. P188 increased brain Aβ burden, potentially through activation of the γ-secretase pathway. Dystrophic neurite pathology was exacerbated in P188 treated mice as indicated by increased LAMP1 accumulation around Aβ deposits. Pathogenic microglial activation was increased by P188. Total tau levels were decreased by P188. Lysosomal enzyme cathepsin D and calcium-dependent vesicular trafficking regulator synaptotagmin-7 (SYT7) were dysregulated upon P188 administration. CONCLUSION P188 brain delivery exacerbated amyloid pathology, dystrophic neurites and pathogenic microglial activation in 5XFAD mice. These effects correlated with lysosomal dysfunction and dysregulation of plasma membrane vesicular trafficking. P188 is not a promising therapeutic strategy against AD pathogenesis.
{"title":"Poloxamer-188 Exacerbates Brain Amyloidosis, Presynaptic Dystrophies, and Pathogenic Microglial Activation in 5XFAD Mice.","authors":"A. Di Meco, Shahrnaz Kemal, J. Popović, S. Chandra, Katherine R. Sadleir, R. Vassar","doi":"10.2174/1567205019666220509143823","DOIUrl":"https://doi.org/10.2174/1567205019666220509143823","url":null,"abstract":"BACKGROUND\u0000Alzheimer's disease (AD) is initiated by aberrant accumulation of amyloid beta (Aβ) protein in the brain parenchyma. The microenvironment surrounding amyloid plaques is characterized by the swelling of presynaptic terminals (dystrophic neurites) associated with lysosomal dysfunction, microtubule disruption and impaired axonal transport. Aβ-induced plasma membrane damage and calcium influx could be potential mechanisms underlying dystrophic neurite formation.\u0000\u0000\u0000OBJECTIVE\u0000We tested whether promoting membrane integrity by brain administration of a safe FDA approved surfactant molecule poloxamer-188 (P188) could attenuate AD pathology in vivo.\u0000\u0000\u0000METHODS\u0000Three-month-old 5XFAD male mice were administered several concentrations of P188 in the brain for 42 days with mini-osmotic pumps. After 42 days, mice were euthanized and assessed for amyloid pathology, dystrophic neurites, pathogenic microglia activation, tau phosphorylation and lysosomal / vesicular trafficking markers in the brain.\u0000\u0000\u0000RESULTS\u0000P188 was lethal at the highest concentration of 10mM. Lower concentrations of P188 (1.2, 12 and 120μM) were well tolerated. P188 increased brain Aβ burden, potentially through activation of the γ-secretase pathway. Dystrophic neurite pathology was exacerbated in P188 treated mice as indicated by increased LAMP1 accumulation around Aβ deposits. Pathogenic microglial activation was increased by P188. Total tau levels were decreased by P188. Lysosomal enzyme cathepsin D and calcium-dependent vesicular trafficking regulator synaptotagmin-7 (SYT7) were dysregulated upon P188 administration.\u0000\u0000\u0000CONCLUSION\u0000P188 brain delivery exacerbated amyloid pathology, dystrophic neurites and pathogenic microglial activation in 5XFAD mice. These effects correlated with lysosomal dysfunction and dysregulation of plasma membrane vesicular trafficking. P188 is not a promising therapeutic strategy against AD pathogenesis.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46048443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-19DOI: 10.2174/1567205019666220419101205
Mohamed H Nafady, Zeinab S Sayed, Dalia A Abdelkawy, Mostafa E Shebl, R. Elsayed, G. Ashraf, Asma Perveen, Mohamed S. Attia, E. Bahbah
It has been hypothesized that the shift in gut microbiota composition, known as gut microbe dysbiosis, may be correlated with the onset of Alzheimer's disease (AD), which is the most common cause of dementia characterized by a gradual deterioration in cognitive function associated with the development of amyloid-beta (Aβ) plaques. The gut microbiota dysbiosis induces the release of significant amounts of amyloids, lipopolysaccharides, and neurotoxins, which might play a role in modulating signaling pathways and immune activation, leading to the production of proinflammatory cytokines related to the pathogenesis of AD. The dysbiosis of gut microbe is associated with various diseases such as type 2 diabetes, obesity, hypertension, and some neuropsychiatric disorders like depression, anxiety, and stress. It is conceivable that these diseases trigger the onset of AD. Thus, modifying the gut microbiota composition with probiotic and prebiotic supplementation can reduce depression and anxiety symptoms, lower stress reactivity, and improve memory. This narrative review aimed to examine the possible role of gut microbe dysbiosis in AD's pathogenesis.
{"title":"The Effect of Gut Microbe Dysbiosis on the Pathogenesis of Alzheimer's Disease (AD) and related conditions.","authors":"Mohamed H Nafady, Zeinab S Sayed, Dalia A Abdelkawy, Mostafa E Shebl, R. Elsayed, G. Ashraf, Asma Perveen, Mohamed S. Attia, E. Bahbah","doi":"10.2174/1567205019666220419101205","DOIUrl":"https://doi.org/10.2174/1567205019666220419101205","url":null,"abstract":"It has been hypothesized that the shift in gut microbiota composition, known as gut microbe dysbiosis, may be correlated with the onset of Alzheimer's disease (AD), which is the most common cause of dementia characterized by a gradual deterioration in cognitive function associated with the development of amyloid-beta (Aβ) plaques. The gut microbiota dysbiosis induces the release of significant amounts of amyloids, lipopolysaccharides, and neurotoxins, which might play a role in modulating signaling pathways and immune activation, leading to the production of proinflammatory cytokines related to the pathogenesis of AD. The dysbiosis of gut microbe is associated with various diseases such as type 2 diabetes, obesity, hypertension, and some neuropsychiatric disorders like depression, anxiety, and stress. It is conceivable that these diseases trigger the onset of AD. Thus, modifying the gut microbiota composition with probiotic and prebiotic supplementation can reduce depression and anxiety symptoms, lower stress reactivity, and improve memory. This narrative review aimed to examine the possible role of gut microbe dysbiosis in AD's pathogenesis.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45758443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-18DOI: 10.2174/1567205019666220418155130
J. Kálmán, D. Devanand, G. Gosztolya, R. Balogh, N. Imre, L. Tóth, I. Hoffmann, Ildikó Kovács, V. Vincze, M. Pákáski
BACKGROUND The development of automatic speech recognition (ASR) technology allows the analysis of temporal (time-based) speech parameters characteristic of mild cognitive impairment (MCI). However, no information has been available on whether the analysis of spontaneous speech can be used with the same efficiency in different language environments. OBJECTIVE The main goal of this international pilot study is to address the question whether the Speech-Gap Test® (S-GAP Test®), previously tested in the Hungarian language, is appropriate for and applicable to the recognition of MCI in other languages such as English. METHOD After an initial screening of 88 individuals, English-speaking (n = 33) and Hungarian-speaking (n = 33) participants were classified as having MCI or as healthy controls (HC) based on Petersen's criteria. Speech of each participant was recorded via a spontaneous speech task. 15 temporal parameters were determined and calculated by means of ASR. RESULTS Seven temporal parameters in the English-speaking sample and 5 in the Hungarian-speaking sample showed significant differences between the MCI and the HC group. Receiver operating characteristics (ROC) analysis clearly distinguished the English-speaking MCI cases from the HC group based on speech tempo and articulation tempo with 100% sensitivity, and on three more temporal parameters with high sensitivity (85.7%). In the Hungarian-speaking sample, the ROC analysis showed similar sensitivity rates (92.3%). CONCLUSION The results of this study in different native-speaking populations suggest that changes in acoustic parameters detected by the S-GAP Test® might be present across different languages.
{"title":"Temporal speech parameters detect mild cognitive impairment in different languages: validation and comparison of the Speech-GAP Test® in English and Hungarian.","authors":"J. Kálmán, D. Devanand, G. Gosztolya, R. Balogh, N. Imre, L. Tóth, I. Hoffmann, Ildikó Kovács, V. Vincze, M. Pákáski","doi":"10.2174/1567205019666220418155130","DOIUrl":"https://doi.org/10.2174/1567205019666220418155130","url":null,"abstract":"BACKGROUND\u0000The development of automatic speech recognition (ASR) technology allows the analysis of temporal (time-based) speech parameters characteristic of mild cognitive impairment (MCI). However, no information has been available on whether the analysis of spontaneous speech can be used with the same efficiency in different language environments.\u0000\u0000\u0000OBJECTIVE\u0000The main goal of this international pilot study is to address the question whether the Speech-Gap Test® (S-GAP Test®), previously tested in the Hungarian language, is appropriate for and applicable to the recognition of MCI in other languages such as English.\u0000\u0000\u0000METHOD\u0000After an initial screening of 88 individuals, English-speaking (n = 33) and Hungarian-speaking (n = 33) participants were classified as having MCI or as healthy controls (HC) based on Petersen's criteria. Speech of each participant was recorded via a spontaneous speech task. 15 temporal parameters were determined and calculated by means of ASR.\u0000\u0000\u0000RESULTS\u0000Seven temporal parameters in the English-speaking sample and 5 in the Hungarian-speaking sample showed significant differences between the MCI and the HC group. Receiver operating characteristics (ROC) analysis clearly distinguished the English-speaking MCI cases from the HC group based on speech tempo and articulation tempo with 100% sensitivity, and on three more temporal parameters with high sensitivity (85.7%). In the Hungarian-speaking sample, the ROC analysis showed similar sensitivity rates (92.3%).\u0000\u0000\u0000CONCLUSION\u0000The results of this study in different native-speaking populations suggest that changes in acoustic parameters detected by the S-GAP Test® might be present across different languages.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44545049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-18DOI: 10.2174/1567205019666220418151914
A. Benmelouka, Yassamine Ouerdane, O. Outani, Y. Alnasser, B. Alghamdi, Asma Perveen, G. Ashraf, M. Ebada
Behavioral and psychotic manifestations, including aggression, delusions, and hallucinations, are frequent comorbidities in patients with debilitating nervous illnesses such as Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Parkinson's disease. AD-related psychosis may be linked to a poor disease prognosis, highlighting that early detection and management are mandatory. The manifestations are variable and may be very heterogeneous, imposing a real diagnostic issue. Some assessment tools such as BEHAVE-AD, CERAD-BRSD, and the Psycho-Sensory Hallucinations Scale have been designed to facilitate the diagnosis. The mechanisms behind neurodegeneration-related psychosis are complex and are not fully understood, imposing a burden on researchers to find appropriate management modalities. Familial history and some genetic disturbances may have a determinant role in these delusions and hallucinations in cases with AD. The loss of neuronal cells, atrophy in some regions of the central nervous, and synaptic dysfunction may also contribute to these comorbidities. Furthermore, inflammatory disturbances triggered by pro-inflammatory agents such as interleukins and tumor necrosis factors are stratified among the potential risk factors of the onset of numerous psychotic symptoms in Alzheimer's patients. Little is known about the possible management tools; therefore, it is urgent to conduct well-designed trials to investigate pharmacological and non-pharmacological interventions that can improve the care process of these patients. This review summarizes the current findings regarding the AD-related psychosis symptoms, pathological features, assessment, and management.
{"title":"Alzheimer's Disease-Related Psychosis: An Overview of Clinical Manifestations, Pathogenesis, and Current Treatment.","authors":"A. Benmelouka, Yassamine Ouerdane, O. Outani, Y. Alnasser, B. Alghamdi, Asma Perveen, G. Ashraf, M. Ebada","doi":"10.2174/1567205019666220418151914","DOIUrl":"https://doi.org/10.2174/1567205019666220418151914","url":null,"abstract":"Behavioral and psychotic manifestations, including aggression, delusions, and hallucinations, are frequent comorbidities in patients with debilitating nervous illnesses such as Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Parkinson's disease. AD-related psychosis may be linked to a poor disease prognosis, highlighting that early detection and management are mandatory. The manifestations are variable and may be very heterogeneous, imposing a real diagnostic issue. Some assessment tools such as BEHAVE-AD, CERAD-BRSD, and the Psycho-Sensory Hallucinations Scale have been designed to facilitate the diagnosis. The mechanisms behind neurodegeneration-related psychosis are complex and are not fully understood, imposing a burden on researchers to find appropriate management modalities. Familial history and some genetic disturbances may have a determinant role in these delusions and hallucinations in cases with AD. The loss of neuronal cells, atrophy in some regions of the central nervous, and synaptic dysfunction may also contribute to these comorbidities. Furthermore, inflammatory disturbances triggered by pro-inflammatory agents such as interleukins and tumor necrosis factors are stratified among the potential risk factors of the onset of numerous psychotic symptoms in Alzheimer's patients. Little is known about the possible management tools; therefore, it is urgent to conduct well-designed trials to investigate pharmacological and non-pharmacological interventions that can improve the care process of these patients. This review summarizes the current findings regarding the AD-related psychosis symptoms, pathological features, assessment, and management.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45099409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-15DOI: 10.2174/1567205019666220415125447
L. Bergantin
BACKGROUND The hypothesis that a dyshomeostasis of Ca2+ increases the incidence of dementia has been established. In fact, several discoveries have emphasized the concept that a decrease of the excess of Ca2+ could be an interesting pharmacological target to alleviate dementia symptoms. Aging along with a healthy brain can be supported by daily exercise, a self-control in caloric ingestion, and participating in intellectually challenging events. These lifestyle factors may alleviate the excess of Ca2+ resulted from a Ca2+ dyshomeostasis. Curiously, epidemiological, and clinical studies have also reported a clinical relationship among hypertension, diabetes and other inflammatory processes, and a higher risk for a decline of cognition. Considering the cumulative data from the scientific literature, including data of high evidence such as meta-analysis and systematic reviews, we can now link a Ca2+ dyshomeostasis as an upstream factor for hypertension, diabetes and other inflammatory processes, and dementia. Several reports have also indicated that increasing cAMP levels may induce neuroprotective outcomes, thus alleviating dementia symptoms. METHODS From these concepts in mind, we found that the pharmacological manipulation of Ca2+/cAMP signalling could be a novel plausible target to treat dementia. This article puts together fundamental concepts, and current therapies, to treat dementia, including novel therapeutics coming from the pharmacological manipulation of Ca2+/cAMP signalling. RESULTS Then, combined with improvements in the lifestyle issues, these novel therapeutics may allow sustained improvements in the life quality of age-related neurological patients. CONCLUSIONS In addition, considering coronavirus disease 2019 (COVID-19) is a rapidly evolving field, this article also reviewed recent reports about the role of Ca2+ channel blockers for restoring Ca2+ signalling disruption due to COVID-19. Finally, this article also presents a timeline of the major events in Ca2+/cAMP signaling.
{"title":"A timeline of Ca2+/cAMP signalling: From basic research to potential therapeutics for dementia.","authors":"L. Bergantin","doi":"10.2174/1567205019666220415125447","DOIUrl":"https://doi.org/10.2174/1567205019666220415125447","url":null,"abstract":"BACKGROUND\u0000The hypothesis that a dyshomeostasis of Ca2+ increases the incidence of dementia has been established. In fact, several discoveries have emphasized the concept that a decrease of the excess of Ca2+ could be an interesting pharmacological target to alleviate dementia symptoms. Aging along with a healthy brain can be supported by daily exercise, a self-control in caloric ingestion, and participating in intellectually challenging events. These lifestyle factors may alleviate the excess of Ca2+ resulted from a Ca2+ dyshomeostasis. Curiously, epidemiological, and clinical studies have also reported a clinical relationship among hypertension, diabetes and other inflammatory processes, and a higher risk for a decline of cognition. Considering the cumulative data from the scientific literature, including data of high evidence such as meta-analysis and systematic reviews, we can now link a Ca2+ dyshomeostasis as an upstream factor for hypertension, diabetes and other inflammatory processes, and dementia. Several reports have also indicated that increasing cAMP levels may induce neuroprotective outcomes, thus alleviating dementia symptoms.\u0000\u0000\u0000METHODS\u0000From these concepts in mind, we found that the pharmacological manipulation of Ca2+/cAMP signalling could be a novel plausible target to treat dementia. This article puts together fundamental concepts, and current therapies, to treat dementia, including novel therapeutics coming from the pharmacological manipulation of Ca2+/cAMP signalling.\u0000\u0000\u0000RESULTS\u0000Then, combined with improvements in the lifestyle issues, these novel therapeutics may allow sustained improvements in the life quality of age-related neurological patients.\u0000\u0000\u0000CONCLUSIONS\u0000In addition, considering coronavirus disease 2019 (COVID-19) is a rapidly evolving field, this article also reviewed recent reports about the role of Ca2+ channel blockers for restoring Ca2+ signalling disruption due to COVID-19. Finally, this article also presents a timeline of the major events in Ca2+/cAMP signaling.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42292383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-14DOI: 10.2174/1567205019666220414101251
Mustafa Doğan, R. Eröz, M. Tecellioğlu, A. Gezdirici, B. Çevik, I. Baris
BACKGROUND Early-onset Alzheimer's disease (EOAD) is commonly diagnosed with an onset age of earlier than 65 years and accounts for 5-10% of all Alzheimer's disease (AD) cases. To date, although only 10-15% of familial EOAD cases have been explained, the genetic cause of the vast proportion of cases has not been explained. The variant Alzheimer's disease with spastic paraparesis (varAD) is defined as a rare clinical entity characterized by early-onset dementia, spasticity of the lower extremities and gait disturbance. Although the disease was first associated with variants in exon 9 of the PSEN1 gene, it was later shown that variations in other exons were also responsible for the disease. OBJECTIVE The current study aims to raise awareness of varAD which occurs as a rare phenotype due to pathogenic variants in PSEN1. In addition, we aimed to evaluate the spectrum of mutations in varAD patients identified to date. METHODS Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family was done by Sanger sequencing. Also, review of the molecularly confirmed patients with (varAD) from the literature was evaluated. RESULTS We identified a heterozygous splicing variant (c.869-1G>A) in the PSEN1 gene, in a family with two affected individuals who present with varAD. We reported the clinical and genetic findings from the affected individuals. CONCLUSION We present the detailed clinical and genetic profiles of a Turkish patient with diagnosis of varAD together with subjects from the literature. Together, we think that the clinical characteristics and the effect of the (c.869-1G>A) variant will facilitate our understanding of the PSEN1 gene in AD pathogenesis.
{"title":"Clinical and Molecular Findings in a Turkish Family Who Had a (c.879-1G>A) Splicing Variant in PSEN1 Gene with A Rare Condition: The Variant Alzheimer's Disease with Spastic Paraparesis.","authors":"Mustafa Doğan, R. Eröz, M. Tecellioğlu, A. Gezdirici, B. Çevik, I. Baris","doi":"10.2174/1567205019666220414101251","DOIUrl":"https://doi.org/10.2174/1567205019666220414101251","url":null,"abstract":"BACKGROUND\u0000Early-onset Alzheimer's disease (EOAD) is commonly diagnosed with an onset age of earlier than 65 years and accounts for 5-10% of all Alzheimer's disease (AD) cases. To date, although only 10-15% of familial EOAD cases have been explained, the genetic cause of the vast proportion of cases has not been explained. The variant Alzheimer's disease with spastic paraparesis (varAD) is defined as a rare clinical entity characterized by early-onset dementia, spasticity of the lower extremities and gait disturbance. Although the disease was first associated with variants in exon 9 of the PSEN1 gene, it was later shown that variations in other exons were also responsible for the disease.\u0000\u0000\u0000OBJECTIVE\u0000The current study aims to raise awareness of varAD which occurs as a rare phenotype due to pathogenic variants in PSEN1. In addition, we aimed to evaluate the spectrum of mutations in varAD patients identified to date.\u0000\u0000\u0000METHODS\u0000Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family was done by Sanger sequencing. Also, review of the molecularly confirmed patients with (varAD) from the literature was evaluated.\u0000\u0000\u0000RESULTS\u0000We identified a heterozygous splicing variant (c.869-1G>A) in the PSEN1 gene, in a family with two affected individuals who present with varAD. We reported the clinical and genetic findings from the affected individuals.\u0000\u0000\u0000CONCLUSION\u0000We present the detailed clinical and genetic profiles of a Turkish patient with diagnosis of varAD together with subjects from the literature. Together, we think that the clinical characteristics and the effect of the (c.869-1G>A) variant will facilitate our understanding of the PSEN1 gene in AD pathogenesis.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42723886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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