Genome‐wide analysis identified abundant genetic modulators of contributions of the apolipoprotein E alleles to Alzheimer's disease risk

2022 ◽  
Author(s):  
Alireza Nazarian ◽  
Yury Loika ◽  
Liang He ◽  
Irina Culminskaya ◽  
Alexander M. Kulminski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Disease Risk ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Genetic Modulators

Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Md. Tanvir Kabir ◽  
Maroua Jalouli ◽  
Md. Ataur Rahman ◽  
Philippe Jeandet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Misfolded Proteins ◽  
Inflammatory Signaling ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Immunological Mechanisms ◽  
The Brain

: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

scholarly journals Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk

2019 ◽  
Vol 51 (3) ◽  
pp. 404-413 ◽  
Author(s):  
Iris E. Jansen ◽  
Jeanne E. Savage ◽  
Kyoko Watanabe ◽  
Julien Bryois ◽  
Dylan M. Williams ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
Meta Analysis ◽  
Genome Wide ◽  
Functional Pathways

scholarly journals Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer's disease

NeuroImage ◽  
2010 ◽  
Vol 51 (2) ◽  
pp. 542-554 ◽  
Author(s):  
Jason L. Stein ◽  
Xue Hua ◽  
Jonathan H. Morra ◽  
Suh Lee ◽  
Derrek P. Hibar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Novel Genes ◽  
Genome Wide Analysis ◽  
Genome Wide

scholarly journals A genome-wide study shows a limited contribution of rare copy number variants to Alzheimer's disease risk

2012 ◽  
Vol 22 (4) ◽  
pp. 816-824 ◽  
Author(s):  
Jade Chapman ◽  
Elliott Rees ◽  
Denise Harold ◽  
Dobril Ivanov ◽  
Amy Gerrish ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Copy Number ◽  
Disease Risk ◽  
Copy Number Variants ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Study

scholarly journals Genetic meta-analysis identifies 9 novel loci and functional pathways for Alzheimer’s disease risk

2018 ◽  
Author(s):  
Iris E Jansen ◽  
Jeanne E Savage ◽  
Kyoko Watanabe ◽  
Julien Bryois ◽  
Dylan M Williams ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Late Onset ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Cell Types ◽  
Mendelian Randomisation ◽  
Genome Wide

AbstractLate onset Alzheimer’s disease (AD) is the most common form of dementia with more than 35 million people affected worldwide, and no curative treatment available. AD is highly heritable and recent genome-wide meta-analyses have identified over 20 genomic loci associated with AD, yet only explaining a small proportion of the genetic variance indicating that undiscovered loci exist. Here, we performed the largest genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 AD cases, 383,378 controls). AD-by-proxy status is based on parental AD diagnosis, and showed strong genetic correlation with AD (rg=0.81). Genetic meta analysis identified 29 risk loci, of which 9 are novel, and implicating 215 potential causative genes. Independent replication further supports these novel loci in AD. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver and microglia). Furthermore, gene-set analyses indicate the genetic contribution of biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomisation results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying more of the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD to guide new drug development.

scholarly journals Genome‐wide analysis of longitudinal Alzheimer’s disease biomarker endophenotypes

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Tanner Y. Jacobson ◽  
Kwangsik Nho ◽  
Shannon L. Risacher ◽  
Sujuan Gao ◽  
Andrew J. Saykin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Analysis ◽  
Disease Biomarker ◽  
Genome Wide

Impacts of apolipoprotein E disclosure on healthy Asian older adults: a cohort study

2019 ◽  
Vol 31 (10) ◽  
pp. 1499-1507
Author(s):  
Wei Theng Sng ◽  
Si Ning Yeo ◽  
Bernice Xiangting Lin ◽  
Tih-Shih Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cohort Study ◽  
Apolipoprotein E ◽  
Disease Risk ◽  
Psychological Symptoms ◽  
Cognitive Activity ◽  
Asian Population ◽  
Asian Populations ◽  
National University

ABSTRACTBackground:The apolipoprotein E (APOE) genotype provides information about Alzheimer’s disease risk, yet genotype disclosure is discouraged due to concerns about possible distress. This is the first study investigating the psychological and behavioral impacts that genetic susceptibility testing for Alzheimer’s disease has in an Asian population.Methods:From March 2016 to November 2017, we ran a prospective cohort study at Duke-National University of Singapore Medical School. 280 healthy Chinese elderly filled in questionnaires that measured psychological symptoms and health behaviors, 1 week before and 6 weeks afterAPOEgenotype disclosure. Responses from ε4-positive subjects (associated with greater Alzheimer’s disease risk) were compared to responses from ε4-negative subjects.Results:ε4 presence was not significantly associated with anxiety (p= 0.09) or depression (p= 0.25). No associations were found for changes to diet (p= 0.36), dietary supplements consumption (p= 0.90), physical activity (p= 0.15), or cognitive activity (p= 0.18).Conclusion:There is no evidence to suggest that disclosure ofAPOEto Asian populations was associated with any short-term adverse psychological or behavioral impacts.

Sign in / Sign up

Export Citation Format

Share Document