Pub Date : 2018-11-01eCollection Date: 2018-01-01DOI: 10.1155/2018/3128758
Corona Solana, Raquel Tarazona, Rafael Solana
Alzheimer's disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.
{"title":"Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer's Disease.","authors":"Corona Solana, Raquel Tarazona, Rafael Solana","doi":"10.1155/2018/3128758","DOIUrl":"10.1155/2018/3128758","url":null,"abstract":"<p><p>Alzheimer's disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (A<i>β</i>). Although A<i>β</i> have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-<i>γ</i> and TNF-<i>α</i> and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"3128758"},"PeriodicalIF":0.0,"publicationDate":"2018-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36741047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-11eCollection Date: 2018-01-01DOI: 10.1155/2018/3149495
Beáta Gavurová, Viliam Kováč, Dominika Jarčušková
Alzheimer's disease-subsequently as AD in the text-represents a chronic neurodegenerative disease discussed very often in the recent period. It involves the G30 diagnosis expressing exactly AD and also the F00 diagnosis epitomising dementia in AD. The Slovak Republic has a very various population in terms of the disparities of the population localisation. The analysis is executed on the basement of the standardised mortality rate. It is calculated for the individual districts of the Slovak Republic to get a detailed spatial view and for each year of the explored period from 1996 to 2015 to get a time development. It has a considerably rising tendency. Therefore, the regional disparities of the standardised mortality rate of AD are analysed from an angle of view of its similarity, by its measurement in a form of a Euclidean distance approach. The results of the analysis offer the heat maps as the distance matrices in a graphic form and the maps of the individual districts too. These outputs reveal a very heterogeneous structure of the standardised mortality rate. Another graphic outcome demonstrates a distribution of its values among the districts throughout the whole Slovak Republic for the whole observed period. The results offer a comparison among the districts of the Slovak Republic too. The highest values and also the lowest values are reached in the different districts for the both sexes. Even, one district reaches the opposite result for the individual sexes. The age structure of the deceased population on the G30 diagnosis is also executed and the extreme values from an angle of a view of the districts are picked up. There are evident high differentiations between the individual districts of the Slovak Republic. The conclusion section involves the several key points and the potential suggestions for further research.
{"title":"Development of Regional Disparities in Alzheimer's Disease Mortality in the Slovak Republic from 1996 to 2015.","authors":"Beáta Gavurová, Viliam Kováč, Dominika Jarčušková","doi":"10.1155/2018/3149495","DOIUrl":"https://doi.org/10.1155/2018/3149495","url":null,"abstract":"<p><p>Alzheimer's disease-subsequently as AD in the text-represents a chronic neurodegenerative disease discussed very often in the recent period. It involves the G30 diagnosis expressing exactly AD and also the F00 diagnosis epitomising dementia in AD. The Slovak Republic has a very various population in terms of the disparities of the population localisation. The analysis is executed on the basement of the standardised mortality rate. It is calculated for the individual districts of the Slovak Republic to get a detailed spatial view and for each year of the explored period from 1996 to 2015 to get a time development. It has a considerably rising tendency. Therefore, the regional disparities of the standardised mortality rate of AD are analysed from an angle of view of its similarity, by its measurement in a form of a Euclidean distance approach. The results of the analysis offer the heat maps as the distance matrices in a graphic form and the maps of the individual districts too. These outputs reveal a very heterogeneous structure of the standardised mortality rate. Another graphic outcome demonstrates a distribution of its values among the districts throughout the whole Slovak Republic for the whole observed period. The results offer a comparison among the districts of the Slovak Republic too. The highest values and also the lowest values are reached in the different districts for the both sexes. Even, one district reaches the opposite result for the individual sexes. The age structure of the deceased population on the G30 diagnosis is also executed and the extreme values from an angle of a view of the districts are picked up. There are evident high differentiations between the individual districts of the Slovak Republic. The conclusion section involves the several key points and the potential suggestions for further research.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"3149495"},"PeriodicalIF":0.0,"publicationDate":"2018-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/3149495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36657460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-09eCollection Date: 2018-01-01DOI: 10.1155/2018/9328293
Fernando Gongora-Rivera, Adolfo Cordero-Perez, Alejandro Gonzalez-Aquines, Antonio Anaya-Escamilla, Eduardo Villarreal-Garza, Meztli Espinosa-Ortega, Mario C Salinas-Carmona, Xochilt Ortiz-Jimenez
Background: Recent studies have shown that cerebral vascularity may be impaired in Alzheimer's disease. Cerebral vasomotor reactivity could be an important biomarker for this pathology.
Aims: The aim of this study was to investigate the alterations in cerebral vascular motor reactivity in Alzheimer's disease subjects and to associate these changes with their cognitive scores.
Methods: We recruited subjects with a diagnosis of Alzheimer's disease and healthy controls. Demographic, clinical, imaging, and cognitive test were obtained. Then all participants performed a cerebral vascular motor reactivity test with 7% CO2 and cerebral blood flow velocities (CBFV) were recorded with transcranial doppler ultrasound before and after the test.
Results: We recruited 45 subjects, 26 (21 female) Alzheimer's disease participants and 19 (15 female) healthy controls. There were no differences in baseline cerebral blood flow velocities between the groups. After the cerebral vasomotor reactivity test, absolute mean difference in mean CBFV (ΔCBFV-m) was 8.70±4.14 versus 4.81±6.96 (p<0.01), respectively. Calculated percentage of change (%CVMR) was lower in the AD group 7.45±18.25 versus 23.29±17.48, and there was a positive but weak correlation with mini-mental scores (ρ=0.337, p=0.023).
Conclusions: In this study, Alzheimer's disease subjects showed significant changes in all absolute cerebral blood flow velocities after the cerebral vasomotor reactivity test with CO2, but only diastolic phase responses were statistically significant. There was a positive but weak correlation between cerebral vasomotor reactivity and cognitive scores. Further studies are needed to investigate these effects in larger Latin-American samples.
背景:最近的研究表明,阿尔茨海默病可能导致脑血管功能受损。脑血管舒缩反应性可能是该病理的重要生物标志物。目的:本研究的目的是研究阿尔茨海默病患者脑血管运动反应性的变化,并将这些变化与他们的认知评分联系起来。方法:我们招募了诊断为阿尔茨海默病的受试者和健康对照者。进行人口学、临床、影像学和认知测试。然后在7% CO2条件下进行脑血管运动反应性测试,测试前后用经颅多普勒超声记录脑血流速度(CBFV)。结果:我们招募了45名受试者,26名阿尔茨海默病患者(21名女性)和19名健康对照者(15名女性)。两组之间的基线脑血流速度没有差异。脑血管舒缩反应性试验后,平均CBFV (ΔCBFV-m)的绝对平均差值为8.70±4.14 vs 4.81±6.96 (p =0.337, p=0.023)。结论:本研究中,阿尔茨海默病患者在CO2脑血管舒缩反应性试验后,所有脑绝对血流速度均有显著变化,但只有舒张期反应有统计学意义。脑血管舒缩反应性与认知评分呈正相关,但相关性较弱。需要进一步的研究在更大的拉丁美洲样本中调查这些影响。
{"title":"Impaired Cerebral Vasomotor Reactivity in Alzheimer's Disease.","authors":"Fernando Gongora-Rivera, Adolfo Cordero-Perez, Alejandro Gonzalez-Aquines, Antonio Anaya-Escamilla, Eduardo Villarreal-Garza, Meztli Espinosa-Ortega, Mario C Salinas-Carmona, Xochilt Ortiz-Jimenez","doi":"10.1155/2018/9328293","DOIUrl":"https://doi.org/10.1155/2018/9328293","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have shown that cerebral vascularity may be impaired in Alzheimer's disease. Cerebral vasomotor reactivity could be an important biomarker for this pathology.</p><p><strong>Aims: </strong>The aim of this study was to investigate the alterations in cerebral vascular motor reactivity in Alzheimer's disease subjects and to associate these changes with their cognitive scores.</p><p><strong>Methods: </strong>We recruited subjects with a diagnosis of Alzheimer's disease and healthy controls. Demographic, clinical, imaging, and cognitive test were obtained. Then all participants performed a cerebral vascular motor reactivity test with 7% CO2 and cerebral blood flow velocities (CBFV) were recorded with transcranial doppler ultrasound before and after the test.</p><p><strong>Results: </strong>We recruited 45 subjects, 26 (21 female) Alzheimer's disease participants and 19 (15 female) healthy controls. There were no differences in baseline cerebral blood flow velocities between the groups. After the cerebral vasomotor reactivity test, absolute mean difference in mean CBFV (ΔCBFV-m) was 8.70±4.14 versus 4.81±6.96 (p<0.01), respectively. Calculated percentage of change (%CVMR) was lower in the AD group 7.45±18.25 versus 23.29±17.48, and there was a positive but weak correlation with mini-mental scores (<i>ρ</i>=0.337, p=0.023).</p><p><strong>Conclusions: </strong>In this study, Alzheimer's disease subjects showed significant changes in all absolute cerebral blood flow velocities after the cerebral vasomotor reactivity test with CO2, but only diastolic phase responses were statistically significant. There was a positive but weak correlation between cerebral vasomotor reactivity and cognitive scores. Further studies are needed to investigate these effects in larger Latin-American samples.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"9328293"},"PeriodicalIF":0.0,"publicationDate":"2018-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/9328293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36539678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-30eCollection Date: 2018-01-01DOI: 10.1155/2018/6852303
Rola Ismail, Allan K Hansen, Peter Parbo, Hans Brændgaard, Hanne Gottrup, David J Brooks, Per Borghammer
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. AD pathology is characterized by abnormal aggregation of the proteins amyloid-β (Aβ) and hyperphosphorylated tau. No effective disease modifying therapies are currently available. A short-duration intervention with 40 Hz light flicker has been shown to reduce brain Aβ load in transgenic mice. We aimed to test the effect of a similar short-duration 40 Hz light flicker regime in human AD patients. We utilized a Light Emitting Diode (LED) light bulb with a 40 Hz flicker. Six Aβ positive patients received 10 days of light therapy, had 2 hours of daily exposure, and underwent a postintervention PiB PET on day 11. After 10 days of light therapy, no significant decrease of PiB SUVR values was detected in any volumes of interest tested (primary visual cortex, visual association cortex, lateral parietal cortex, precuneus, and posterior cingulate) or in the total motor cortex, and longer treatments may be necessary to induce amyloid removal in humans.
{"title":"The Effect of 40-Hz Light Therapy on Amyloid Load in Patients with Prodromal and Clinical Alzheimer's Disease.","authors":"Rola Ismail, Allan K Hansen, Peter Parbo, Hans Brændgaard, Hanne Gottrup, David J Brooks, Per Borghammer","doi":"10.1155/2018/6852303","DOIUrl":"10.1155/2018/6852303","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder. AD pathology is characterized by abnormal aggregation of the proteins amyloid-<i>β</i> (A<i>β</i>) and hyperphosphorylated tau. No effective disease modifying therapies are currently available. A short-duration intervention with 40 Hz light flicker has been shown to reduce brain A<i>β</i> load in transgenic mice. We aimed to test the effect of a similar short-duration 40 Hz light flicker regime in human AD patients. We utilized a Light Emitting Diode (LED) light bulb with a 40 Hz flicker. Six A<i>β</i> positive patients received 10 days of light therapy, had 2 hours of daily exposure, and underwent a postintervention PiB PET on day 11. After 10 days of light therapy, no significant decrease of PiB SUVR values was detected in any volumes of interest tested (primary visual cortex, visual association cortex, lateral parietal cortex, precuneus, and posterior cingulate) or in the total motor cortex, and longer treatments may be necessary to induce amyloid removal in humans.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"6852303"},"PeriodicalIF":0.0,"publicationDate":"2018-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36439007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-02eCollection Date: 2018-01-01DOI: 10.1155/2018/3280621
Kelly Estrada-Orozco, Kely Bonilla-Vargas, Francy Cruz, Oscar Mancera, Miguel Ruiz, Laura Alvarez, Rodrigo Pardo, Humberto Arboleda
Introduction: Cognitive disorders are a clinical and research challenge; in particular, the mild cognitive disorder (MiCD) requires diagnostic suspicion and tools with adequate performance for its detection. The objective of this study was the validation of a short cognitive test (CATest) for the detection of MiCD in population of 50 years or more.
Methods: A diagnostic accuracy study was assembled and performed in a prospective cohort. A consecutive sample of 200 Colombian subjects who represented the whole spectrum of the condition of interest allowed us to reach the objective. Validity was determined by concurrent criteria. The cut points were determined by the ROC curves considering the best overall performance and accuracy of the test.
Results: CATest was validated to detection of MiCD at a cut-off point of 18. As a result, scores lower than 18 classified the participants as MiCD. At this cut-off point, CATest showed sensitivity of 84.3% (CI 76 to 90.16), specificity of 71.4% (CI 95% 61.8 to 79.43), positive predictive value of 75% ( 95% CI 66.79 to 82.42), and area under curve AUC 0.8518 (standard error SE 0.0265).
Discussion: CATest has an adequate performance as a short cognitive test for the detection of MiCD. Its performance is superior to MiniMental and similar to Montreal Cognitive test (MoCA) according to the data reported in the literature. The advantages over other tests are the evaluation of all cognitive domains, time of application, and easy interpretation of results. CATest is a free use alternative for MiCD detection.
引言:认知障碍是一项临床和研究挑战;特别是,轻度认知障碍(MiCD)需要诊断怀疑和具有足够性能的检测工具。本研究的目的是验证一种短认知测试(CATest)在50岁或以上人群中检测MiCD的有效性。方法:在前瞻性队列中进行诊断准确性研究。连续抽样200名哥伦比亚受试者,他们代表了所有感兴趣的条件,使我们能够达到目标。有效性由并发标准确定。切割点由ROC曲线确定,考虑测试的最佳整体性能和准确性。结果:CATest在截断点为18的情况下能够检测到MiCD。因此,得分低于18分的参与者被归类为MiCD。在该截止点,CATest的敏感性为84.3% (CI 76 ~ 90.16),特异性为71.4% (CI 95% 61.8 ~ 79.43),阳性预测值为75% (95% CI 66.79 ~ 82.42),曲线下面积AUC为0.8518(标准误差SE 0.0265)。讨论:CATest作为一种简短的认知测试,在检测MiCD方面有足够的表现。从文献数据来看,其性能优于MiniMental,与Montreal Cognitive test (MoCA)相近。与其他测试相比,其优点是评估所有认知领域,应用时间短,结果易于解释。CATest是一种免费的MiCD检测替代品。
{"title":"Cognitive Assessment Test: Validation of a Short Cognitive Test for the Detection of Mild Cognitive Disorder.","authors":"Kelly Estrada-Orozco, Kely Bonilla-Vargas, Francy Cruz, Oscar Mancera, Miguel Ruiz, Laura Alvarez, Rodrigo Pardo, Humberto Arboleda","doi":"10.1155/2018/3280621","DOIUrl":"https://doi.org/10.1155/2018/3280621","url":null,"abstract":"<p><strong>Introduction: </strong>Cognitive disorders are a clinical and research challenge; in particular, the mild cognitive disorder (MiCD) requires diagnostic suspicion and tools with adequate performance for its detection. The objective of this study was the validation of a short cognitive test (CATest) for the detection of MiCD in population of 50 years or more.</p><p><strong>Methods: </strong>A diagnostic accuracy study was assembled and performed in a prospective cohort. A consecutive sample of 200 Colombian subjects who represented the whole spectrum of the condition of interest allowed us to reach the objective. Validity was determined by concurrent criteria. The cut points were determined by the ROC curves considering the best overall performance and accuracy of the test.</p><p><strong>Results: </strong>CATest was validated to detection of MiCD at a cut-off point of 18. As a result, scores lower than 18 classified the participants as MiCD. At this cut-off point, CATest showed sensitivity of 84.3% (CI 76 to 90.16), specificity of 71.4% (<b>CI</b> 95% 61.8 to 79.43), positive predictive value of 75% ( 95% CI 66.79 to 82.42), and area under curve AUC 0.8518 (standard error SE 0.0265).</p><p><strong>Discussion: </strong>CATest has an adequate performance as a short cognitive test for the detection of MiCD. Its performance is superior to MiniMental and similar to Montreal Cognitive test (MoCA) according to the data reported in the literature. The advantages over other tests are the evaluation of all cognitive domains, time of application, and easy interpretation of results. CATest is a free use alternative for MiCD detection.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"3280621"},"PeriodicalIF":0.0,"publicationDate":"2018-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/3280621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36354327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibodies against many neural antigens are detected in the sera of both patients with Alzheimer's disease (AD) and some healthy individuals. Blood-brain barrier dysfunction could make it possible for brain-reactive autoantibodies to reach the brain, where they can react with amyloid ß peptide (AßP). The origin of these autoreactive antibodies in the blood is unclear. The goals of this study were as follows: (1) to examine the immune reactivity of anti-AßP-42 with 22 neuronal and other associated antigens, some of which are involved in the pathophysiology of AD; (2) to classify antibodies to these 22 different antigens into those that cross-react with AßP-42 and those that do not; (3) to determine whether these antibodies react with BBB proteins, nerve growth factors, and enteric neuronal antigens. Using monoclonal AßP-42 antibody and ELISA methodology, we found that the antibody was highly reactive with Aß protein, tau protein, presenilin, rabaptin-5, β-NGF, BDNF, mTG, and enteric nerve. The same antibody produced equivocal to moderate reactions with glutamate-R, S100B, AQP4, GFAP, MBP, α-synuclein, tTG-2, and tTG-3, and not with the rest. These antibodies were also measured in blood samples from 47 AD patients and 47 controls. IgG antibodies were found to be elevated against AßP-42 and many other antigens in a significant percentage of controls. Overall, the mean OD values were significantly higher against 9/23 tested antigens (p <0.001) in the samples with AD. We were indeed able to classify the detected neuronal antibodies into those that cross-react with AßP-42 and those that do not. Our main finding is that although these antibodies may be harmless in a subgroup of controls, in individuals with compromised BBBs these antibodies that cross-react with AßP-42 can reach the brain, where their cross-reactivity with AßP-42 may contribute to the onset and progression of AD, and perhaps other neurodegenerative disorders.
{"title":"Amyloid-Beta 1-42 Cross-Reactive Antibody Prevalent in Human Sera May Contribute to Intraneuronal Deposition of A-Beta-P-42.","authors":"Aristo Vojdani, Elroy Vojdani","doi":"10.1155/2018/1672568","DOIUrl":"10.1155/2018/1672568","url":null,"abstract":"<p><p>Antibodies against many neural antigens are detected in the sera of both patients with Alzheimer's disease (AD) and some healthy individuals. Blood-brain barrier dysfunction could make it possible for brain-reactive autoantibodies to reach the brain, where they can react with amyloid ß peptide (AßP). The origin of these autoreactive antibodies in the blood is unclear. The goals of this study were as follows: (1) to examine the immune reactivity of anti-AßP-42 with 22 neuronal and other associated antigens, some of which are involved in the pathophysiology of AD; (2) to classify antibodies to these 22 different antigens into those that cross-react with AßP-42 and those that do not; (3) to determine whether these antibodies react with BBB proteins, nerve growth factors, and enteric neuronal antigens. Using monoclonal AßP-42 antibody and ELISA methodology, we found that the antibody was highly reactive with Aß protein, tau protein, presenilin, rabaptin-5, <i>β</i>-NGF, BDNF, mTG, and enteric nerve. The same antibody produced equivocal to moderate reactions with glutamate-R, S100B, AQP4, GFAP, MBP, <i>α</i>-synuclein, tTG-2, and tTG-3, and not with the rest. These antibodies were also measured in blood samples from 47 AD patients and 47 controls. IgG antibodies were found to be elevated against AßP-42 and many other antigens in a significant percentage of controls. Overall, the mean OD values were significantly higher against 9/23 tested antigens (<i>p</i> <0.001) in the samples with AD. We were indeed able to classify the detected neuronal antibodies into those that cross-react with AßP-42 and those that do not. Our main finding is that although these antibodies may be harmless in a subgroup of controls, in individuals with compromised BBBs these antibodies that cross-react with AßP-42 can reach the brain, where their cross-reactivity with AßP-42 may contribute to the onset and progression of AD, and perhaps other neurodegenerative disorders.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"1672568"},"PeriodicalIF":0.0,"publicationDate":"2018-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/1672568","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36335538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cognitive performance is an important endophenotype for various neurodegenerative and neuropsychiatric traits. In the present study two genetic variants in the leucine-zipper protein (LUZP2) and the F-box 40 protein (FBXO40) genes, previously reported to be genome-wide significant for Alzheimer's diseases and schizophrenia, were examined for an association with cognitive abilities in normal elderly from the Russian population. Rs1021261 in the LUZP2 and rs3772130 in the FBXO40 were genotyped by multiplex PCR and MALDI-TOF mass spectrometry in a sample of 708 normal elderly subjects tested for cognitive performance using the Montreal Cognitive Assessment (MoCA). Association of genetic variability with the MoCA scores was estimated by parametric and nonparametric analysis of variance and by the frequency comparison between upper and lower quartiles of MoCA distribution. Significantly higher frequency of "TT" genotype of rs1021261 in the LUZP2 gene as well as "A" allele and "AA" genotype of rs3772130 in the FBXO40 gene was found in a subsample of individuals with the MoCA score less than 20 comparing to the fourth quartile's subsample (MoCA > 25). The data of the present study suggests that genetic variability in the LUZP2 and FBXO40 loci associated with neurodegenerative and neuropsychiatric diseases is also contributed to the normal variability in cognitive performance in the elderly.
{"title":"Analysis of Association of Genetic Markers in the LUZP2 and FBXO40 Genes with the Normal Variability in Cognitive Performance in the Elderly.","authors":"Vadim Stepanov, Kseniya Vagaitseva, Anna Bocharova, Andrey Marusin, Valentina Markova, Larisa Minaycheva, Oksana Makeeva","doi":"10.1155/2018/2686045","DOIUrl":"https://doi.org/10.1155/2018/2686045","url":null,"abstract":"<p><p>Cognitive performance is an important endophenotype for various neurodegenerative and neuropsychiatric traits. In the present study two genetic variants in the leucine-zipper protein (LUZP2) and the F-box 40 protein (FBXO40) genes, previously reported to be genome-wide significant for Alzheimer's diseases and schizophrenia, were examined for an association with cognitive abilities in normal elderly from the Russian population. Rs1021261 in the LUZP2 and rs3772130 in the FBXO40 were genotyped by multiplex PCR and MALDI-TOF mass spectrometry in a sample of 708 normal elderly subjects tested for cognitive performance using the Montreal Cognitive Assessment (MoCA). Association of genetic variability with the MoCA scores was estimated by parametric and nonparametric analysis of variance and by the frequency comparison between upper and lower quartiles of MoCA distribution. Significantly higher frequency of \"TT\" genotype of rs1021261 in the LUZP2 gene as well as \"A\" allele and \"AA\" genotype of rs3772130 in the FBXO40 gene was found in a subsample of individuals with the MoCA score less than 20 comparing to the fourth quartile's subsample (MoCA > 25). The data of the present study suggests that genetic variability in the LUZP2 and FBXO40 loci associated with neurodegenerative and neuropsychiatric diseases is also contributed to the normal variability in cognitive performance in the elderly.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"2686045"},"PeriodicalIF":0.0,"publicationDate":"2018-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/2686045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36179151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-31eCollection Date: 2018-01-01DOI: 10.1155/2018/7608038
Robert P Weinberg, Vera V Koledova, Hyeari Shin, Jennifer H Park, Yew Ai Tan, Anthony J Sinskey, Ravigadevi Sambanthamurthi, ChoKyun Rha
Alzheimer's disease is a severe neurodegenerative disease characterized by the aggregation of amyloid-β peptide (Aβ) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of Aβ42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that Aβ42 aggregation is inhibited in vitro by oil palm phenolics (OPP), an aqueous extract from the oil palm tree (Elaeis guineensis). The data shows that OPP inhibits stacking of β-pleated sheets, which is essential for oligomerization. We demonstrate the inhibition of Aβ42 aggregation by (1) mass spectrometry; (2) Congo Red dye binding; (3) 2D-IR spectroscopy; (4) dynamic light scattering; (5) transmission electron microscopy; and (6) transgenic yeast rescue assay. In the yeast rescue assay, OPP significantly reduces the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. The data shows that OPP inhibits (1) the aggregation of Aβ into oligomers; (2) stacking of β-pleated sheets; and (3) fibrillar growth and coalescence. These inhibitory effects prevent the formation of neurotoxic oligomers and hold potential as a means to reduce neuroinflammation and neuronal death and thereby may play some role in the prevention or treatment of Alzheimer's disease.
{"title":"Oil Palm Phenolics Inhibit the <i>In Vitro</i> Aggregation of <i>β</i>-Amyloid Peptide into Oligomeric Complexes.","authors":"Robert P Weinberg, Vera V Koledova, Hyeari Shin, Jennifer H Park, Yew Ai Tan, Anthony J Sinskey, Ravigadevi Sambanthamurthi, ChoKyun Rha","doi":"10.1155/2018/7608038","DOIUrl":"https://doi.org/10.1155/2018/7608038","url":null,"abstract":"<p><p>Alzheimer's disease is a severe neurodegenerative disease characterized by the aggregation of amyloid-<i>β</i> peptide (A<i>β</i>) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of A<i>β</i>42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that A<i>β</i>42 aggregation is inhibited <i>in vitro</i> by oil palm phenolics (OPP), an aqueous extract from the oil palm tree <i>(Elaeis guineensis)</i>. The data shows that OPP inhibits stacking of <i>β</i>-pleated sheets, which is essential for oligomerization. We demonstrate the inhibition of A<i>β</i>42 aggregation by (1) mass spectrometry; (2) Congo Red dye binding; (3) 2D-IR spectroscopy; (4) dynamic light scattering; (5) transmission electron microscopy; and (6) transgenic yeast rescue assay. In the yeast rescue assay, OPP significantly reduces the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. The data shows that OPP inhibits (1) the aggregation of A<i>β</i> into oligomers; (2) stacking of <i>β</i>-pleated sheets; and (3) fibrillar growth and coalescence. These inhibitory effects prevent the formation of neurotoxic oligomers and hold potential as a means to reduce neuroinflammation and neuronal death and thereby may play some role in the prevention or treatment of Alzheimer's disease.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2018 ","pages":"7608038"},"PeriodicalIF":0.0,"publicationDate":"2018-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/7608038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36019527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-03-01DOI: 10.1155/2017/5479597
Alba Sierra-Marcos
Alzheimer's disease (AD) depicts dynamic changes in regional brain function from early stages of the disease. Arterial spin labeling- (ASL-) based MRI methods have been applied for detecting regional cerebral blood flow (rCBF) perfusion changes in patients with AD and mild cognitive impairment (MCI). Nevertheless, the results obtained from ASL studies in AD and MCI are still controversial, since rCBF maps may show both hypoperfusion or hyperperfusion areas in brain structures involved in different cognitive functions. The goal of this review is to provide the current state of the art regarding the role of ASL for detecting distinctive perfusion patterns in subjects with MCI and/or AD. The ability to obtain this information using a noninvasive and widely available modality such as ASL should greatly enhance the knowledge into the broad range of hemodynamically related changes taking place during the cognitive decline process in AD.
{"title":"Regional Cerebral Blood Flow in Mild Cognitive Impairment and Alzheimer's Disease Measured with Arterial Spin Labeling Magnetic Resonance Imaging.","authors":"Alba Sierra-Marcos","doi":"10.1155/2017/5479597","DOIUrl":"https://doi.org/10.1155/2017/5479597","url":null,"abstract":"<p><p>Alzheimer's disease (AD) depicts dynamic changes in regional brain function from early stages of the disease. Arterial spin labeling- (ASL-) based MRI methods have been applied for detecting regional cerebral blood flow (rCBF) perfusion changes in patients with AD and mild cognitive impairment (MCI). Nevertheless, the results obtained from ASL studies in AD and MCI are still controversial, since rCBF maps may show both hypoperfusion or hyperperfusion areas in brain structures involved in different cognitive functions. The goal of this review is to provide the current state of the art regarding the role of ASL for detecting distinctive perfusion patterns in subjects with MCI and/or AD. The ability to obtain this information using a noninvasive and widely available modality such as ASL should greatly enhance the knowledge into the broad range of hemodynamically related changes taking place during the cognitive decline process in AD.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2017 ","pages":"5479597"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/5479597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35054608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-12-05DOI: 10.1155/2017/2438901
Mark E McCaulley, Kira A Grush
There is no effective etiologic treatment for Alzheimer's disease, nor is there a prophylactic medication which delays or prevents its onset. The lack of an accurate paradigm is undoubtedly related to the lack of effective means of prophylaxis and treatment. The current paradigm of beta amyloid in Alzheimer's brains causing cognitive dysfunction must be modified. Despite failed clinical trials, research continues into amyloid-oriented treatments. The persistence of the amyloid hypothesis/paradigm is an example of anchoring and representativeness heuristics described by Kahneman and Tversky in their classic 1974 Science paper. Economic factors also contribute to the persistence of this paradigm. Paradigms impact the scientific process by the following: (1) what is studied; (2) the types of questions that are asked; (3) the structure and nature of the questions; (4) the interpretations of research findings. We review the contribution of inflammation, malfunction of the neurovascular unit, and prion disease to Alzheimer's disease manifestations. Any or all of these are candidates for inclusion into a more accurate, inclusive, and useful new paradigm. By incorporating emerging facts and understanding into a new paradigm, we will enhance our ability to move toward effective prophylaxis and therapy for this tragic disease.
{"title":"Seeking a New Paradigm for Alzheimer's Disease: Considering the Roles of Inflammation, Blood-Brain Barrier Dysfunction, and Prion Disease.","authors":"Mark E McCaulley, Kira A Grush","doi":"10.1155/2017/2438901","DOIUrl":"10.1155/2017/2438901","url":null,"abstract":"<p><p>There is no effective etiologic treatment for Alzheimer's disease, nor is there a prophylactic medication which delays or prevents its onset. The lack of an accurate paradigm is undoubtedly related to the lack of effective means of prophylaxis and treatment. The current paradigm of beta amyloid in Alzheimer's brains causing cognitive dysfunction must be modified. Despite failed clinical trials, research continues into amyloid-oriented treatments. The persistence of the amyloid hypothesis/paradigm is an example of anchoring and representativeness heuristics described by Kahneman and Tversky in their classic 1974 <i>Science</i> paper. Economic factors also contribute to the persistence of this paradigm. Paradigms impact the scientific process by the following: (1) what is studied; (2) the types of questions that are asked; (3) the structure and nature of the questions; (4) the interpretations of research findings. We review the contribution of inflammation, malfunction of the neurovascular unit, and prion disease to Alzheimer's disease manifestations. Any or all of these are candidates for inclusion into a more accurate, inclusive, and useful new paradigm. By incorporating emerging facts and understanding into a new paradigm, we will enhance our ability to move toward effective prophylaxis and therapy for this tragic disease.</p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2017 ","pages":"2438901"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35757741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}