Introduction: Variation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (eg, a non-APOE polygenic risk score [PRS]) may interact with the APOE ε4 allele to influence cognitive decline.
Methods: We tested the PRS × APOE ε4 × age interaction on preclinical cognition using longitudinal data from the Wisconsin Registry for Alzheimer's Prevention. All analyses were fitted using a linear mixed-effects model and adjusted for within individual/family correlation among 1190 individuals.
Results: We found statistically significant PRS × APOE ε4 × age interactions on immediate learning (P = 0.038), delayed recall (P < 0.001), and Preclinical Alzheimer's Cognitive Composite 3 score (P = 0.026). PRS-related differences in overall and memory-related cognitive domains between people with and without APOE ε4 emerge around age 70, with a much stronger adverse PRS effect among APOE ε4 carriers. The findings were replicated in a population-based cohort.
Discussions: APOE ε4 can modify the association between PRS and cognition decline.
Highlights: APOE ε4 can modify the association between polygenic risk scores (PRSs) and longitudinal cognition decline, with the modifying effects more pronounced when the PRS is constructed using a conservative P threshold (eg, P < 5 ). The adverse genetic effect caused by the combined effect of the currently known genetic variants is more detrimental among APOE ε4 carriers around age 70. Individuals who are APOE ε4 carriers with high PRSs are the most vulnerable to the harmful effects caused by genetic burden.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916952 | PMC |
| http://dx.doi.org/10.1002/alz.13515 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Non-APOE variants predominately expressed in smooth muscle cells contribute to the influence of Alzheimer's disease genetic risk on white matter hyperintensities.
Alzheimers Dement
December 2024
Department of Psychology, University of Bath, Bath, UK.
Introduction: White matter hyperintensity volumes (WMHVs) are disproportionally prevalent in individuals with Alzheimer's disease (AD), potentially reflecting neurovascular injury. We quantify the association between AD polygenic risk score (AD-PRS) and WMHV, exploring single-nucleotide polymorphisms (SNPs) that are proximal to genes overexpressed in cerebrovascular cell species.
Methods: In a UK-Biobank sub-sample (mean age = 64, range = 45-81 years), we associate WMHV with (1) AD-PRS estimated via SNPs across the genome (minus apolipoprotein E [APOE] locus) and (2) AD-PRS estimated with SNPs proximal to specific genes that are overexpressed in cerebrovascular cell species.
Association of polygenic risk scores with Alzheimer's disease and plasma biomarkers among Chinese older adults: A community-based study.
Alzheimers Dement
October 2024
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.
Introduction: We examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population.
Methods: This population-based study used baseline data from MIND-China (2018; n = 4873) and follow-up data from dementia-free individuals (2014-2018; n = 2117). We measured AD-related plasma biomarkers in a subsample (n = 1256).
Mid-to-Late Life Healthy Lifestyle Modifies Genetic Risk for Longitudinal Cognitive Aging among Asymptomatic Individuals.
medRxiv
May 2024
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University.
Importance: Genetic and lifestyle factors contribute to an individual's risk of developing Alzheimer's disease. However, it is unknown whether and how adherence to healthy lifestyles can mitigate the genetic risk of Alzheimer's.
Objective: The aim of this study is to investigate whether adherence to healthy lifestyles can modify the impact of genetic predisposition to Alzheimer's disease on later-life cognitive decline.
Polygenic risk scores for Alzheimer's disease in relation to cognitive change: A representative sample from the general population followed over 16 years.
Neurobiol Dis
December 2023
Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden. Electronic address:
Background: Polygenic risk scores for Alzheimer's disease (AD-PRSs) have been associated with cognition. However, few studies have examined the effect of AD-PRS beyond the APOE gene, and the influence of genetic variants related to level of cognitive ability (COG-PRS) on cognitive performance over time in the general older population.
Method: A population-based sample of 965 individuals born in 1930, with genetic and standardized cognitive data on six psychometric tests (Thurstone's picture memory, immediate recall of 10 words, Block design, word fluency, figure identification, delayed recall of 12 items), were examined at age 70, 75, 79, and 85 years.
Apolipoprotein E moderates the association between non-APOE polygenic risk score for Alzheimer's disease and aging on preclinical cognitive function.
Alzheimers Dement
February 2024
Department of Population Health Science, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Introduction: Variation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (eg, a non-APOE polygenic risk score [PRS]) may interact with the APOE ε4 allele to influence cognitive decline.
Methods: We tested the PRS × APOE ε4 × age interaction on preclinical cognition using longitudinal data from the Wisconsin Registry for Alzheimer's Prevention. All analyses were fitted using a linear mixed-effects model and adjusted for within individual/family correlation among 1190 individuals.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!