Current Alzheimer research最新文献

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with a significant burden on global health. AD is characterized by a progressive cognitive decline and memory loss. Emerging research suggests a potential link between periodontitis, specifically the presence of oral bacteria such as Porphyromonas gingivalis (P. gingivalis), and AD progression. P. gingivalis produces an enzyme, Agmatine deiminase (AgD), which converts agmatine to N-carbamoyl putrescine (NCP), serving as a precursor to essential polyamines. Recent studies have confirmed the correlation between disruptions in polyamine metabolism and cognitive impairment.

Objective: This study aims to investigate the dysregulation of P. gingivalis Agmatine deiminase (PgAgD) in the context of AD.

Methods: Saliva samples were collected from a total of 54 individuals, including 27 AD patients and 27 healthy controls. The expression of the PgAgD gene was analyzed using quantitative Real-- Time PCR.

Results: The results showed a significant decrease in PgAgD gene expression in the saliva samples of AD patients compared to healthy controls. This downregulation was found in AD patients with advanced stages of periodontitis. Additionally, a correlation was observed between the decrease in PgAgD expression and the 30-item Mini-Mental State Examination (MMSE) score.

Conclusion: These findings suggest that measuring PgAgD expression in saliva could be a noninvasive tool for monitoring AD progression and aid in the early diagnosis of patients with periodontitis. Further research is needed to validate our results and explore the underlying mechanisms linking periodontitis, PgAgD expression, and AD pathophysiology.

Background: Neurodegenerative disorders like Alzheimer's disease (AD) involve the abnormal aggregation of tau protein, which forms toxic oligomers and amyloid deposits. The structure of tau protein is influenced by the conformational states of distinct proline residues, which are regulated by peptidyl-prolyl isomerases (PPIases). However, there has been no research on the impact of human cyclophilin A (CypA) as a PPIase on (non-phosphorylated) tau protein aggregation.

Methods: On the basis of these explanations, we used various spectroscopic techniques to explore the effects of CypA on tau protein aggregation behavior.

Results: We demonstrated the role of the isomerization activity of CypA in promoting the formation of tau protein amyloid fibrils with well-defined and highly ordered cross-β structures. According to the "cistauosis hypothesis," CypA's ability to enhance tau protein fibril formation in AD is attributed to the isomerization of specific proline residues from the trans to cis configuration. To corroborate this theory, we conducted refolding experiments using lysozyme as a model protein. The presence of CypA increased lysozyme aggregation and impeded its refolding process. It is known that proper refolding of lysozyme relies on the correct (trans) isomerization of two critical proline residues.

Conclusion: Thus, our findings confirmed that CypA induces the trans-to-cis isomerization of specific proline residues, ultimately leading to increased aggregation. Overall, this study highlights the emerging role of isomerization in tau protein pathogenesis in AD.

Introduction: The Corpus Callosum (CC) is the largest commissural tract in the nervous system. Few studies have examined the extent of CC in Alzheimer's disease (AD) patients, and these studies have reported conflicting findings.

Materials and methods: The study was performed using 176 brain MRI images of 88 Alzheimer's patients (55 women-32 men) and 88 healthy individuals (44 women-44 men).

Results: In our study, 7 different parameters of the CC were measured, and their average values were determined. We measured each parameter separately in AD patients and healthy individuals and compared them with each other.

Conclusion: CC has an important place not only in Patients with AD but also in other neurodegenerative diseases. We consider that our study will be useful in the evaluation of Patients with AD.

Background: Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of Flemingia vestita (FV) phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment.

Materials and methods: Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes.

Results: 8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions.

Discussion: The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology.

Conclusion: 8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability.

Introduction/objective: Age-related cognitive decline has been linked with risk factors, including physical performance. Prior studies investigating such associations were typically conducted in clinical settings within Western populations with a frequent focus on late neurocognitive diagnostic stages (i.e., Alzheimer's disease), reducing their generalizability to the Asian population and early neurocognitive stages. To address these knowledge gaps, our study investigated longitudinal associations between physical performance measures at baseline and cognitive change in global cognition, executive functioning (EF) based and non-executive functioning (non- EF) based cognitive domains within the Singaporean population. The moderating role of early neurocognitive status, namely mild cognitive impairment (MCI) and cognitively normal (CN), was also examined.

Methods: This paper examined data from 347 participants (CN = 284; MCI = 63) who participated in the Community Health and Intergenerational (CHI) study at baseline and follow-up. Data from a neurocognitive battery and three physical performance tests, namely the timed-up and go (TUG), fast gait speed (FGS) and 30-second chair-stand test (30s-CST), were analysed using multivariate linear regression models.

Results: Only one significant association between FGS scores and cognitive change in Semantic Fluency was observed; other associations were not significant. Cognitive status also significantly moderated associations between TUG/30s-CST tasks with several neurocognitive tests.

Conclusion: The lack of significant longitudinal associations between baseline physical performance measures and cognitive change differed from findings in the literature. Nevertheless, the moderating role of cognitive status further highlighted the need to account for cognitive status when exploring such associations within a heterogeneous group of older adults without dementia.

Background: Due to the heterogeneity of Alzheimer's disease (AD), the underlying pathogenic mechanisms have not been fully elucidated. Oligodendrocyte (OL) damage and myelin degeneration are prevalent features of AD pathology. When oligodendrocytes are subjected to amyloid-beta (Aβ) toxicity, this damage compromises the structural integrity of myelin and results in a reduction of myelin-associated proteins. Consequently, the impairment of myelin integrity leads to a slowdown or cessation of nerve signal transmission, ultimately contributing to cognitive dysfunction and the progression of AD. Consequently, elucidating the relationship between oligodendrocytes and AD from the perspective of oligodendrocytes is instrumental in advancing our understanding of the pathogenesis of AD.

Objective: Here, an attempt is made in this study to identify oligodendrocyte-related biomarkers of AD.

Methods: AD datasets were obtained from the Gene Expression Omnibus database and used for consensus clustering to identify subclasses. Hub genes were identified through differentially expressed genes (DEGs) analysis and oligodendrocyte gene set enrichment. Immune infiltration analysis was conducted using the CIBERSORT method. Signature genes were identified using machine learning algorithms and logistic regression. A diagnostic nomogram for predicting AD was developed and validated using external datasets and an AD model. A small molecular compound was identified using the eXtreme Sum algorithm.

Results: 46 genes were found to be significantly correlated with AD progression by examining the overlap between DEGs and oligodendrocyte genes. Two subclasses of AD, Cluster A, and Cluster B, were identified, and 9 signature genes were identified using a machine learning algorithm to construct a nomogram. Enrichment analysis showed that 9 genes are involved in apoptosis and neuronal development. Immune infiltration analysis found differences in immune cell presence between AD patients and controls. External datasets and RT-qPCR verification showed variation in signature genes between AD patients and controls. Five small molecular compounds were predicted.

Conclusion: It was found that 9 oligodendrocyte genes can be used to create a diagnostic tool for AD, which could help in developing new treatments.

Background: Creutzfeldt-Jakob disease (CJD) is a fatal degenerative brain disease characterized by rapidly progressive dementia. Sporadic CJD (sCJD) is the best-known and most common subtype. Because the disease is uncommon and has highly diverse presenting symptoms, early diagnosis is challenging. We herein report a case of probable sCJD diagnosed at a very early stage.

Case presentation: A 61-year-old female patient had mild attention and memory problems for a few months that were noticed by her husband but did not bother her and did not affect her daily life activities. The first brain magnetic resonance imaging (MRI) at another hospital was normal, lacking diffusion-weighted imaging (DWI). Although the newly taken brain MRI without DWI was normal, the patient's husband brought his patient to our outpatient clinic because he continued to think that there was a difference in his wife's attention and memory. A neurological examination of the patient revealed almost normal findings. The neuropsychiatric evaluation of the patient was consistent with mild cognitive impairment. The patient's electroencephalography taken upon admission had no characteristic findings for CJD but showed generalized epileptiform activity. Therefore, the patient was hospitalized, and a second brain MRI, including DWI sequences, was performed. DWI displayed bilateral asymmetrical typical patterns of restricted diffusion. Cerebrospinal fluid 14-3-3 was positive, and total-tau was highly elevated. She had a diagnosis of probable sCJD at an early stage. Later, the patient developed progressive dementia, ataxia, seizures, and extrapyramidal symptoms, followed by mutism, and died.

Conclusion: Although there is no cure for CJD today, early diagnosis is essential, mainly because of its potential infectivity and for future planning. Diagnosing sCJD in its early stages is difficult. However, taking into account the observations of not only the patient's history but also their longterm partners in cognitive evaluations will be helpful in making an early and accurate diagnosis.

Background: Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.

Objectives: We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Methods: AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Results: In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Conclusion: Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.

Background: Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases.

Objective: This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1) and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and healthy controls.

Methods: Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units and 22 healthy controls. Diagnostic evaluations followed established criteria and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods.

Results: Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls.

Conclusion: The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.