The Potential of ‘Omics to Link Lipid Metabolism and Genetic and Comorbidity Risk Factors of Alzheimer’s Disease in African Americans

Author(s):  
Kaitlyn E. Stepler ◽  
Renã A. S. Robinson
2006 ◽  
Vol 14 (7S_Part_6) ◽  
pp. P339-P339
Author(s):  
Olivia J. Conway ◽  
Minerva M. Carrasquillo ◽  
Jenny M. Bredenberg ◽  
Joseph S. Reddy ◽  
Curtis S. Younkin ◽  
...  

2020 ◽  
Author(s):  
Yejin Kim ◽  
Sean I Savitz ◽  
Jessica Lee ◽  
Paul E Schulz ◽  
Luyao Chen ◽  
...  

Objectives: To investigate risk factors for progression to Alzheimer's disease and related dementias (ADRD) in African Americans and non-Hispanic Caucasians in a large US cohort. Design: A matched case-control design using electronic health records (EHRs) from 2000 - 2017. Setting: Cerner EHRs database covering more than 600 Cerner client hospitals. Participants: 79,120 patients aged 65 and older (#ADRD=39,560, #non ADRD older adults=39,560) from an initial cohort of 49,826,000 patients. Measurements: We converted ICD9 or ICD10 diagnosis codes into PheWas codes to increase clinical relevance. Then we detected ADRD as having both ADRD diagnosis codes and medications. We considered PheWas codes for Alzheimer's disease, dementia with cerebral degenerations, senile dementia, and vascular dementia. We considered ADRD medications including acetylcholine and memantine. Results: Using two-step propensity score matching, we built an African American cohort of 4,429 and a 4,570-person matched Caucasian cohort that was similar in terms of onset age, observation length, sex, and known ADRD risks (diabetes, vascular disease, heart disease, head injury, and obesity). Older African Americans had a statistically significant progression from cerebrovascular risk (transient ischemic attack) to ADRD incidence (treatment effect coefficient = 0.0978, p-value <0.000) whereas the matched Caucasians did not (treatment effect coefficient = 0.403, p-value = 0.196). Conclusion: Our extensive causal analysis using a nationwide EHR discovered disease progression pathways to ADRD. The carefully matched cohorts from different racial groups showed different progression, which partly explains the racial disparities in ADRD incidence.


2006 ◽  
Vol 21 (2-3) ◽  
pp. 224-229 ◽  
Author(s):  
A. Ogunniyi ◽  
K. S. Hall ◽  
O. Gureje ◽  
O. Baiyewu ◽  
S. Gao ◽  
...  

2019 ◽  
Vol 72 (3) ◽  
pp. 919-929 ◽  
Author(s):  
Lindsay R. Clark ◽  
Derek Norton ◽  
Sara E. Berman ◽  
Sterling C. Johnson ◽  
Barbara B. Bendlin ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1215 ◽  
Author(s):  
Francisco Sáez-Orellana ◽  
Jean-Noël Octave ◽  
Nathalie Pierrot

Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. Mutations in genes encoding proteins involved in amyloid-β peptide (Aβ) production are responsible for inherited AD cases. The amyloid cascade hypothesis was proposed to explain the pathogeny. Despite the fact that Aβ is considered as the main culprit of the pathology, most clinical trials focusing on Aβ failed and suggested that earlier interventions are needed to influence the course of AD. Therefore, identifying risk factors that predispose to AD is crucial. Among them, the epsilon 4 allele of the apolipoprotein E gene that encodes the major brain lipid carrier and metabolic disorders such as obesity and type 2 diabetes were identified as AD risk factors, suggesting that abnormal lipid metabolism could influence the progression of the disease. Among lipids, fatty acids (FAs) play a fundamental role in proper brain function, including memory. Peroxisome proliferator-activated receptor α (PPARα) is a master metabolic regulator that regulates the catabolism of FA. Several studies report an essential role of PPARα in neuronal function governing synaptic plasticity and cognition. In this review, we explore the implication of lipid metabolism in AD, with a special focus on PPARα and its potential role in AD therapy.


2000 ◽  
Vol 21 ◽  
pp. 158
Author(s):  
Neill R. Graff-Radford ◽  
Jennifer Adamson ◽  
Floyd B. Willis ◽  
Dawn E. Epstein ◽  
R. LaShaune Lawson ◽  
...  

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