Recent Advances in Synaptosomal Proteomics in Alzheimer’s Disease

: The current meta-analysis of the cohort review was designed to elucidate the progress made in neuroproteomics of the synaptosome. The association of the comprehensive synaptic proteome and its link to physiological or pathological settings is rapidly mounting. Chemical synapses in the brain are focal hot spots for interneuronal signaling, signal transduction, and plasticity. Structurally, synapses comprise axon termini or the presynapse (vesicles filled with neurotransmitters that function as molecular signals), synaptic clefts (extracellular matrix and adhesion molecules), and post-synaptic density or PSD (with receptors for neurotransmitters that rely upon the chemical signaling). The pre- and post-synaptic clefts are responsible for mediating and regulating neurotransmitter release Their receptor binding and perception rely on chemical signals. Moreover, short- and long-term structural and functional alterations that are necessary for the optimal higher-order brain functions are also mainly dependent on the protein dynamics at the synapses. Not surprisingly, disruptions in synaptic physiology are considered as the major pathogenic mechanisms underlying the progression of several neurodegenerative disorders, including Alzheimer's disease. This review briefly discusses the subcellular fractionation protocols and the related biochemical approaches for the isolation of synaptic compartments. Besides, it discusses the progress made in understanding the pathological alterations in the synaptic proteome in neurodegenerative disorders, particularly focussing on Alzheimer's disease dementia.

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Use of CSF α-synuclein in the differential diagnosis between Alzheimer's disease and other neurodegenerative disorders

International Psychogeriatrics ◽

10.1017/s1041610215000447 ◽

2015 ◽

Vol 27 (9) ◽

pp. 1429-1438 ◽

Cited By ~ 18

Author(s):

Zheng-Yu Wang ◽

Zhen-Min Han ◽

Qi-Fei Liu ◽

Wei Tang ◽

Kui Ye ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Differential Diagnosis ◽

Neurodegenerative Disorders ◽

Meta Analysis ◽

Lewy Bodies ◽

Cochrane Library ◽

Random Effects Models ◽

Significant Difference ◽

Meta Analyses

ABSTRACTBackground:The etiology and pathogenesis of neurodegenerative disorders has yet to be elucidated, so their differential diagnosis is a challenge. This is especially true in differentiating Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA).Methods:A total of 11 eligible articles were identified by search of electronic databases including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June 2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence intervals (CI), comparing cerebrospinal fluid (CSF) measures of α-synuclein between the above conditions were calculated using random-effects models.Results:CSF α-synuclein concentrations were significantly higher in AD compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD: 0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI: (0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found between patients with AD and neurological cognitively normal controls [SMD: 0.02, 95% CI: (−0.21, 0.24), z = 0.13, P = 0.894].Conclusions:Results of these meta-analysis suggest that quantification of CSF α-synuclein could help distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.

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A Meta-Analysis Study on Alzheimer’s Disease

Journal of Bioscience & Biomedical Engineering ◽

10.47485/2693-2504.1050 ◽

2021 ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Treatment Guidelines ◽

Meta Analysis ◽

Disease Treatment ◽

Preventative Measures ◽

Long Run ◽

New Treatments ◽

New Evidence ◽

Made In

To gather and assess information on Alzheimer’s disease and its treatment from published studies to depict the overall treatment effect. The metaphysical findings appear to indicate that Alzheimer’s disease has multiple causes. There have been reports of patients reporting different symptoms or causing different symptoms. Treatments and preventative measures, on the other hand, have historically been difficult to implement. There has been no clear evidence as to which drug or treatment will clearly reduce the severity of this disease until now. Scientists have created drugs and treatments that can aid in the prevention and treatment of patients who have recently been diagnosed with the disease. As a result, there is a good chance that the treatment will improve and eventually be able to fully cure Alzheimer’s patients. Over the last two decades, enormous progress has been made in understanding Alzheimer’s disease, including its diagnosis, treatment pattern, epidemiology, and economic impact. Alzheimer’s disease is one of the most incapacitating old-age diseases. Thanks to a thorough understanding of the disease’s natural history, we were able to develop appropriate trial designs and outcomes for the various stages of Alzheimer’s disease. Alzheimer’s disease treatment guidelines must be constantly updated to reflect new evidence in order to benefit patients and caregivers in the long run. As the population ages, the availability of new treatments for Alzheimer’s disease management, as well as changes in the health-care system, will necessitate the integration of existing knowledge in order to better meet the needs of Alzheimer’s patients and their families.

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Repurposing Immunomodulatory Imide Drugs (IMiDs) in Neuropsychiatric and Neurodegenerative Disorders

Frontiers in Neuroscience ◽

10.3389/fnins.2021.656921 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yoo Jin Jung ◽

David Tweedie ◽

Michael T. Scerba ◽

Dong Seok Kim ◽

Maria Francesca Palmas ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Neurodegenerative Disorders ◽

Neurological Disorders ◽

Meta Analysis ◽

Inflammatory Factors ◽

Sample Type ◽

Post Traumatic Stress

Neuroinflammation represents a common trait in the pathology and progression of the major psychiatric and neurodegenerative disorders. Neuropsychiatric disorders have emerged as a global crisis, affecting 1 in 4 people, while neurological disorders are the second leading cause of death in the elderly population worldwide (WHO, 2001; GBD 2016 Neurology Collaborators, 2019). However, there remains an immense deficit in availability of effective drug treatments for most neurological disorders. In fact, for disorders such as depression, placebos and behavioral therapies have equal effectiveness as antidepressants. For neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, drugs that can prevent, slow, or cure the disease have yet to be found. Several non-traditional avenues of drug target identification have emerged with ongoing neurological disease research to meet the need for novel and efficacious treatments. Of these novel avenues is that of neuroinflammation, which has been found to be involved in the progression and pathology of many of the leading neurological disorders. Neuroinflammation is characterized by glial inflammatory factors in certain stages of neurological disorders. Although the meta-analyses have provided evidence of genetic/proteomic upregulation of inflammatory factors in certain stages of neurological disorders. Although the mechanisms underpinning the connections between neuroinflammation and neurological disorders are unclear, and meta-analysis results have shown high sensitivity to factors such as disorder severity and sample type, there is significant evidence of neuroinflammation associations across neurological disorders. In this review, we summarize the role of neuroinflammation in psychiatric disorders such as major depressive disorder, generalized anxiety disorder, post-traumatic stress disorder, and bipolar disorder, as well as in neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease, and introduce current research on the potential of immunomodulatory imide drugs (IMiDs) as a new treatment strategy for these disorders.

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Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer’s Disease

Journal of Clinical Medicine ◽

10.3390/jcm10143009 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3009

Author(s):

Maciej Dulewicz ◽

Agnieszka Kulczyńska-Przybik ◽

Agnieszka Słowik ◽

Renata Borawska ◽

Barbara Mroczko

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Fatty Acid ◽

Lipid Metabolism ◽

Neurodegenerative Disorders ◽

Study Cohort ◽

Fatty Acid Binding ◽

Brain Functions

Background: Lipid metabolism-related biomarkers gain increasing researchers interest in the field of neurodegenerative disorders. Mounting evidence have indicated the role of fatty acid-binding proteins and pathology lipid metabolism in Alzheimer’s Disease (AD). The imbalance of fatty acids (FA) and lipids may negatively affect brain functions related to neurodegenerative disorders. The ApoE4 and FABP3 proteins may reflect processes leading to neurodegeneration. This study aimed to evaluate the relationship between the CSF levels of FABP3 and ApoE4 proteins and cognitive decline as well as the diagnostic performance of these candidate biomarkers in AD and mild cognitive impairment (MCI). Methods: A total of 70 subjects, including patients with AD, MCI, and non-demented controls, were enrolled in the study. CSF concentrations of FABP3 and ApoE4 were measured using immunoassay technology. Results: Significantly higher CSF concentrations of FABP3 and ApoE4 were observed in AD patients compared to MCI subjects and individuals without cognitive impairment. Both proteins were inversely associated with Aβ42/40 ratio: ApoE4 (rho = −0.472, p < 0.001), and FABP3 (rho = −0.488, p < 0.001) in the whole study group, respectively. Additionally, FABP3 was negatively correlated with Mini-Mental State Examination score in the whole study cohort (rho = −0.585 p < 0.001). Conclusion: Presented results indicate the pivotal role of FABP3 and ApoE4 in AD pathology as lipid-related biomarkers, but studies on larger cohorts are needed.

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Supplemental Material for Risk of Progression to Alzheimer’s Disease for Different Neuropsychological Mild Cognitive Impairment Subtypes: A Hierarchical Meta-Analysis of Longitudinal Studies

Psychology and Aging ◽

10.1037/pag0000294.supp ◽

2018 ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Longitudinal Studies ◽

Meta Analysis ◽

Risk Of Progression

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Faculty Opinions recommendation of Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718009150.793476303 ◽

2013 ◽

Author(s):

Craig Ritchie ◽

Abel Koshy

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Studies ◽

Vascular Dementia ◽

Meta Analysis ◽

Late Life ◽

Late Life Depression ◽

Community Based

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Effect of antihypertensive drugs on cognition and behavioral symptoms of patients with Alzheimer’s disease: A meta-analysis

Current Pharmaceutical Biotechnology ◽

10.2174/1386207323666201211101720 ◽

2020 ◽

Vol 21 ◽

Author(s):

Roja Rahimi ◽

Shekoufeh Nikfar ◽

Masoud Sadeghi ◽

Mohammad Abdollahi ◽

Reza Heidary Moghaddam ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Randomized Clinical Trials ◽

Antihypertensive Drugs ◽

Meta Analysis ◽

Behavioral Symptoms ◽

Cochrane Library ◽

Mean Differences ◽

Global Impression Of Change ◽

State Examination

Background: It has been found that there is a link between hypertension and elevated risk of Alzheimer’s disease (AD). Herein, a meta-analysis based on randomized clinical trials (RCTs) was used to assess the effect of antihypertensive drugs on cognition and behavioral symptoms of AD patients. Method: The three databases – PubMed/Medline, Scopus, and Cochrane Library- were searched up to March 2020. The quality of the studies included in the meta-analysis was evaluated by the Jadad score. Clinical Global Impression of Change (CGIC) included in two studies, Mini-Mental State Examination (MMSE) included in three studies, and Neuropsychiatric Inventory (NPI) in three studies were the main outcomes in this systematic review. Results: Out of 1506 studies retrieved in the databases, 5 RCTs included and analyzed in the meta-analysis. The pooled mean differences of CGIC, MMSE, and NPI in patients with AD receiving antihypertensive drugs compared to placebo was -1.76 with (95% CI = -2.66 to -0.86; P=0.0001), 0.74 (95% CI = 0.20 to 1.28; P= 0.007), and -9.49 (95% CI = -19.76 to 0.79; P = 0.07), respectively. Conclusion: The findings of the present meta-analysis show that antihypertensive drugs may improve cognition and behavioral symptoms of patients with AD. However, more well-designed RCTs with similar drugs are needed to achieve more conclusive results.

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Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

Current Alzheimer Research ◽

10.2174/1567205015666180119105446 ◽

2018 ◽

Vol 15 (7) ◽

pp. 610-617 ◽

Cited By ~ 4

Author(s):

Huifeng Zhang ◽

Dan Liu ◽

Huanhuan Huang ◽

Yujia Zhao ◽

Hui Zhou

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enzyme Activity ◽

Protein Level ◽

Senile Plaque ◽

Meta Analysis ◽

Cochrane Library ◽

Insulin Degrading Enzyme ◽

Degrading Enzyme ◽

Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

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Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205017666200317092310 ◽

2020 ◽

Vol 17 (2) ◽

pp. 141-157 ◽

Cited By ~ 2

Author(s):

Dubravka S. Strac ◽

Marcela Konjevod ◽

Matea N. Perkovic ◽

Lucija Tudor ◽

Gordana N. Erjavec ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Large Scale ◽

Therapeutic Potential ◽

Relevant Literature ◽

Comprehensive Overview ◽

Brain Functions ◽

Specific Effects ◽

And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

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