Current Alzheimer research最新文献

Alzheimer's disease (AD) is the most common type of dementia, pathologically characterized by the accumulation of senile plaques and neurofibrillary tangles. Chronic kidney disease (CKD) is highly prevalent in the elderly population closely associated with the occurrence of dementia. Recent epidemiological and experimental studies suggest a potential association of CKD with AD. Both diseases share a panel of identical risk factors, such as type 2 diabetes and hypertension. However, the relationship between CKD and AD is unclear. Lower clearance of a panel of uremic toxin including cystatin- C, guanidine, and adiponectin due to CKD is implied to contribute to AD pathogenesis. In this review, we summarize the current evidence from epidemiological, experimental, and clinical studies on the potential contribution of uremic toxins to AD pathogenesis. We describe outstanding questions and propose an outlook on the link between uremic toxins and AD.

Background: Neuroimaging suggests that white matter microstructure is severely affected in Alzheimer's disease (AD) progression. However, whether alterations in white matter microstructure are confined to specific regions and whether they can be used as potential biomarkers to distinguish normal control (NC) from AD are unknown.

Methods: In this cross-sectional study, 33 cases of AD and 25 cases of NC were recruited for automatic fiber quantification (AFQ). A total of 20 fiber bundles were equally divided into 100 segments for quantitative assessment of fractional anisotropy (FA), mean diffusivity (MD), volume and curvature. In order to further evaluate the diagnostic value, the maximum redundancy minimum (mRMR) and LASSO algorithms were used to select features, calculate the Radscore of each subject, establish logistic regression models, and draw ROC curves, respectively, to assess the predictive power of four different models.

Results: There was a significant increase in the MD values in AD patients compared with healthy subjects. The differences were mainly located in the left cingulum hippocampus (HCC), left uncinate fasciculus (UF) and superior longitudinal fasciculus (SLF). The point-wise level of 20 fiber bundles was used as a classification feature, and the MD index exhibited the best performance to distinguish NC from AD.

Conclusion: These findings contribute to the understanding of the pathogenesis of AD and suggest that abnormal white matter based on DTI-based AFQ analysis is helpful to explore the pathogenesis of AD.

Background: Alzheimer's disease (AD) is the most common form of dementia in the elderly population and places heavy burdens on medical care and nursing. Recently, the psychiatric and behavioral symptoms of prodromal AD, especially mild behavioral impairment (MBI), have attracted much attention. In 2012, Alzheimer's Association International Conference, MBI was proposed as a syndrome with psychiatric and behavioral disturbance before the onset of typical clinical cognitive symptoms in dementia. Increasing lines of evidence have indicated the link between MBI and early AD pathologies including Aβ and tau.

Objective: This narrative review aims to summarize the advantages of MBI over other concept of psychiatric and behavioral symptoms associated with AD in the early prediction of AD dementia. We also discuss the possible common genetic basis and pathological mechanisms underlying the interactions between MBI and AD.

Methods: Papers cited here were retrieved from PubMed up to February 2022. We selected a total of 95 articles for summary and discussion.

Results: The occurrence of MBI is mainly due to the overlapped genetic and pathological risk factors with AD and is related to the brain's response to environmental stressors. MBI may be a warning sign for the early pathology of AD, and more attention should be paid on the number and duration of MBI symptoms.

Conclusion: MBI may be an early sign and predictor of Alzheimer's disease dementia. Early intervention for MBI may have a positive effect on alleviating long-term cognitive decline.

Down Syndrome (DS), caused by triplication of human chromosome 21 (Hsa21) is the most common form of intellectual disability worldwide. Recent progress in healthcare has resulted in a dramatic increase in the lifespan of individuals with DS. Unfortunately, most will develop Alzheimer's disease like dementia (DS-AD) as they age. Understanding similarities and differences between DSAD and the other forms of the disease - i.e., late-onset AD (LOAD) and autosomal dominant AD (ADAD) - will provide important clues for the treatment of DS-AD. In addition to the APP gene that codes the precursor of the main component of amyloid plaques found in the brain of AD patients, other genes on Hsa21 are likely to contribute to disease initiation and progression. This review focuses on SYNJ1, coding the phosphoinositide phosphatase synaptojanin 1 (SYNJ1). First, we highlight the function of SYNJ1 in the brain. We then summarize the involvement of SYNJ1 in the different forms of AD at the genetic, transcriptomic, proteomic and neuropathology levels in humans. We further examine whether results in humans correlate with what has been described in murine and cellular models of the disease and report possible mechanistic links between SYNJ1 and the progression of the disease. Finally, we propose a set of questions that would further strengthen and clarify the role of SYNJ1 in the different forms of AD.

Background: Quantitative measures of atrophy on structural MRI are sensitive to the neurodegeneration that occurs in AD, and the topographical pattern of atrophy could serve as a sensitive and specific biomarker.

Objective: We aimed to examine the distribution of cortical atrophy associated with cognitive decline and disease stage based on quantitative structural MRI analysis in a Chinese cohort to inform clinical diagnosis and follow-up of AD patients.

Methods: One hundred and eleven patients who were clinically diagnosed with probable AD were enrolled. All patients completed a systemic cognitive evaluation and domain-specific batteries. The severity of cognitive decline was defined by MMSE score: 1-10 severe, 11-20 moderate, and 21-30 mild. Cortical volume and thickness determined using 3D-T1 MRI data were analyzed using voxelbased morphometry and surface-based analysis supported by the DR. Brain Platform.

Results: The male:female ratio was 38:73. The average age was 70.8 ± 10.6 years. The mild: moderate: severe ratio was 48:38:25. Total grey matter volume was significantly related to cognition while the relationship between white matter volume and cognition did not reach statistical significance. The volume of the temporal-parietal-occipital cortex was most strongly associated with cognitive decline in group analysis, while the hippocampus and entorhinal area had a less significant association with cognitive decline. Volume of subcortical grey matter was also associated with cognition. Volume and thickness of temporoparietal cortexes were significantly correlated with the cognitive decline, with a left predominance observed.

Conclusion: Cognitive deterioration was associated with cortical atrophy. Volume and thickness of the left temporal-parietal-occipital cortex were most important in early diagnosis and longitudinal evaluation of AD in clinical practice. Cognitively relevant cortices were left predominant.

In the next few years, the prevalence of diabetes mellitus (DM) is projected to dramatically increase globally, but most of the cases will occur in low-to-middle-income countries. Some of the major risk factors for diabetes accelerate the development of dementia in African-Americans, thus leading to a higher prevalence of dementia than Caucasians. Sub-Saharian Africa women have a disproportionately two-to-eight fold increased prevalence of dementia. In the eye of this storm, Nigeria holds the highest number of diabetics on the African continent, and its prevalence is rising in parallel to obesity, hypertension, and the population's aging. The socio-economic impact of the rising prevalence of DM and dementia will be huge and unsustainable for the healthcare system in Nigeria, as has been recognized in developed economies. Here, we analyze the current situation of women's health in Nigeria and explore future perspectives and directions. The complex interplay of factors involved in diabetes and dementia in Nigerian women include key biological agents (metabolic syndrome, vascular damage, inflammation, oxidative stress, insulin resistance), nutritional habits, lifestyle, and anemia, that worsen with comorbidities. In addition, restricted resources, lack of visibility, and poor management result in a painful chain that increases the risk and burden of disease in Nigerian women from youth to old ages. Heath policies to increase the ratio of mental health professionals per number of patients, mostly in rural areas, foment of proactive primary care centers, and interventions targeting adolescents and adult women and other specific mothers-children pairs are strongly required for a sustainable development goal.

Objective: The aim of the present work was to investigate the features of the elderly population aged ≥65 yrs and with deteriorative mild cognitive impairment (MCI) due to Alzheimer's disease (AD) to establish a prediction model.

Methods: A total of 105 patients aged ≥65 yrs and with MCI were followed up, with a collection of 357 features, which were derived from the demographic characteristics, hematological indicators (serum Aβ1-40, Aβ1-42, P-tau and MCP-1 levels, APOE gene), and multimodal brain Magnetic Resonance Imaging (MRI) imaging indicators of 116 brain regions (ADC, FA and CBF values). Cognitive function was followed up for 2 yrs. Based on the Python platform Anaconda, 105 patients were randomly divided into a training set (70%) and a test set (30%) by analyzing all features through a random forest algorithm, and a prediction model was established for the form of rapidly deteriorating MCI.

Results: Of the 105 patients enrolled, 41 deteriorated, and 64 did not come within 2 yrs. Model 1 was established based on demographic characteristics, hematological indicators and multi-modal MRI image features, the accuracy of the training set being 100%, the accuracy of the test set 64%, sensitivity 50%, specificity 67%, and AUC 0.72. Model 2 was based on the first five features (APOE4 gene, FA value of left fusiform gyrus, FA value of left inferior temporal gyrus, FA value of left parahippocampal gyrus, ADC value of right calcarine fissure as surrounding cortex), the accuracy of the training set being 100%, the accuracy of the test set 85%, sensitivity 91%, specificity 80% and AUC 0.96. Model 3 was based on the first four features of Model 1, the accuracy of the training set is 100%, the accuracy of the test set 97%, sensitivity100%, specificity 95% and AUC 0.99. Model 4 was based on the first three characteristics of Model 1, the accuracy of the training set being 100%, the accuracy of the test set 94%, sensitivity 92%, specificity 94% and AUC 0.96. Model 5 was based on the hematological characteristics, the accuracy of the training set is 100%, the accuracy of the test set 91%, sensitivity 100%, specificity 88% and AUC 0.97. The models based on the demographic characteristics, imaging characteristics FA, CBF and ADC values had lower sensitivity and specificity.

Conclusion: Model 3, which has four important predictive characteristics, can predict the rapidly deteriorating MCI due to AD in the community.

Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer's Disease (AD), with the prominent presence of reactive astrocytes surrounding amyloid-β plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demonstrated that astrocytes from AD brains are different from "normal" healthy astrocytes, showing dysregulations in areas such as neurotransmitter recycling, including glutamate and GABA, and impaired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology, worsening of the inflammatory profile, and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal models has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD.

Background: The effect that cytokines can exert on the progression from mild cognitive impairment (MCI) to ongoing dementia is a matter of debate and the results obtained so far are controversial.

Objective: The aim of the study is to analyze the influence of markers of subclinical inflammation on the progression of MCI to dementia.

Methods: A prospective study involving a cohort of patients ≥ 65 years of age diagnosed with MCI and followed for 3 years was conducted. 105 patients were enrolled, and serum concentrations of several subclinical inflammatory markers were determined.

Results: After 3.09 (2 - 3.79) years of follow-up, 47 (44.76%) patients progressed to dementia. Alpha 1-antichymotrypsin (ACT) was found to be significantly higher in patients who progressed to dementia (486.45 ± 169.18 vs. 400.91 ± 163.03; p = 0.012), and observed to significantly increase the risk of developing dementia in patients with mild cognitive impairment (1.004, 1.001-1.007; p = 0.007). IL-10 levels were significantly higher in those who remained stable (6.69 ± 18.1 vs. 32.54 ± 89.6; p = 0.04). Regarding the type of dementia to which our patients progressed, we found that patients who developed mixed dementia had higher IL-4 levels than those who converted to AD (31.54 ± 63.6 vs. 4.43 ± 12.9; p = 0.03). No significant differences were observed between the groups with regard to the ESR and LPa, CRP, IL-1 and TNF-α levels.

Conclusion: ACT levels have a significant predictive value in the conversion of MCI to dementia. IL-10 levels could be a protective factor. It is necessary to conduct studies with serial determinations of these and other inflammatory markers in order to determine their effect on the progression of MCI to dementia.

Alzheimer's disease is a progressive and deadly neurodegenerative disorder and one of the most common causes of dementia globally. Current, insufficiently sensitive and specific methods of early diagnosing and monitoring this disease prompt a search for new tools. Numerous literature data have indicated that the pathogenesis of Alzheimer's disease (AD) is not limited to the neuronal compartment but involves various immunological mechanisms. Neuroinflammation has been recognized as a very important process in AD pathology. It seems to play pleiotropic roles, both neuroprotective and neurodegenerative, in the development of cognitive impairment depending on the stage of the disease. Mounting evidence demonstrates that inflammatory proteins could be considered biomarkers of disease progression. Therefore, the present review summarizes the role of some inflammatory molecules and their potential utility in detecting and monitoring dementia severity. This paper also provides a valuable insight into new mechanisms leading to the development of dementia, which might be useful in discovering possible anti-inflammatory treatment.