Aging / Alzheimer's
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30803
Browse
Browsing Aging / Alzheimer's by Author "Housini, Mohammad"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Alzheimer's Disease Risk Allele Frequencies Differ Based on Ethnicity in HABLE Cohort(2022) Housini, Mohammad; Rao, Sumedha; Phillips, Nicole; O'Bryant, Sid; Barber, Robert C.Purpose: Alzheimer's Disease (AD) or other related dementias remain a significant burden on our aging population. Here we evaluate the top 10 AD risk alleles previously reported by Kunkle et al. (2018) in Mexican Americans and non-Hispanic whites enrolled in the Healthy Aging Brain in Latino Elders Study (HABLE) cohort to see if allele frequencies vary based on ethnicity. Methods: DNA was extracted from buffy coat samples (n = 1635) on the Hamilton robotic system with the Mag-Bind Blood & Tissue DNA HDQ 96 Kit. Genotyping was performed per manufacturer's protocol using the Illumina Infinium Global Screening Array (GSA) and analyzed with Genome Studio 2.0. Samples with call rates less than 98% were repeated or excluded. Allele and genotype frequencies were calculated using standard statistics by compiling the top ten AD risk alleles from Kunkle et al. (2018) and measuring their frequencies in the HABLE cohort. Results: Our data suggest varying degrees of allele and genotype frequencies among the top 10 risk conferring SNPs between Mexican Americans and Non-Hispanic Whites. In particular, we show some instances (BIN1, PTK2B) where the heterozygotes are in higher frequency than homozygotes. 8 of our evaluated SNPs show a difference greater than 5% between the two ethnicities. Conclusion: It may be beneficial to further study the top AD risk alleles among different ethnicities to determine if there are variable frequencies in those populations. We plan to expand and continue this work in other ethnicities and further elaborate on these differences to promote ethnicity targeted diagnostics and help reduce health disparities in medicine and science.Item Studying the Interplay Between Baseline Mental Health and Alzheimer's Disease Progression(2022) Rao, Sumedha; Housini, Mohammad; Royall, Donald; Palmer, Raymond; Barber, Robert C.Background: In aging adults, the most common form of dementia is Alzheimer's disease (AD). AD pathogenesis involves the accumulation of beta-amyloid (Aβ) protein aggregation in plaques and tau proteins in neurofibrillary tangles that are associated with a decreased number of synapses in the brain, altered neuronal function and cell death via neurotoxicity, as well as learning and memory deficits. Clinically, the presence and severity of neuropsychiatric symptoms that AD patients present with can be reliably measured by the Neuropsychiatric Inventory Questionnaire (NPIQ). This study aims to explore the association between baseline mental health and the severity of AD progression. Methods: To measure baseline mental health, NPIQ scores were used while the change in DeltaEq was used to represent the severity of AD progression within the TARCC cohort. DeltaEq is a homolog of Delta, a reliable latent dementia proxy that represents cognitive correlates of functional status and is specific for distinguishing cases with AD from other dementia-related presentations. Most crucially, the DeltaEq homolog has been adjusted for equivalence across ethnicities. Using stratified analysis and structured equation models, the association between baseline mental health and change in was investigated. Results: The first model exploring NPIQ and the change in DeltaEq was only adjusted for baseline eq; it showed NPIQ explaining 19% of the variance in delta DeltaEq and was statistically significant at p=0.016 for Non-Hispanic Whites. With the second model, age, sex, and education were adjusted for in addition to baseline eq. NPIQ was shown to explain 25% of the variance in delta DeltaEq while being statistically significant at p=0.037 for Non-Hispanic Whites. This model was replicated in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort; NPIQ was shown to be predictive for delta DeltaEq at p=0.013. Conclusion: In Non-Hispanic Whites, worse baseline mental health has been shown to predict increased severity and progression of AD. This makes it a clinical therapeutic target with the possible benefit of impacting the course of AD in patients. The fascinating interplay between mental health and its relationship to Alzheimer's disease should be studied further with an additional focus on ethnicity.