Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease
Derek B Archer1,2, Jaclyn M Eissman1,2, Shubhabrata Mukherjee3
1Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|November 20, 2023
Summary
This study identified novel genetic variants and genes influencing late-life memory performance and decline. These findings highlight shared genetic underpinnings between memory and other health traits.
Area of Science:
- Genetics
- Neuroscience
- Aging Research
Background:
- Genome-wide association studies (GWAS) have advanced Alzheimer's disease (AD) research, but few have focused on continuous memory performance and decline.
- Understanding the genetic basis of memory is crucial for developing targeted interventions for cognitive aging.
Purpose of the Study:
- To conduct a cross-ancestry GWAS on memory performance and memory decline.
- To identify novel genetic loci, genes, and correlations associated with late-life memory.
- To explore the shared genetic architecture of memory with AD, neuropsychiatric, and autoimmune traits.
Main Methods:
- Leveraged harmonized cognitive data from four aging cohorts.
- Performed cross-ancestry GWAS on memory performance (N=27,633) and memory decline (N=22,365).
- Conducted gene-level analysis and assessed genetic correlations.
Main Results:
- Identified high heritability for memory performance and decline across ancestries.
- Discovered a novel locus for memory decline (rs6848524) and three loci for memory performance in specific ancestry groups.
- Found novel genes for memory decline (SLC25A44, BSX, DPP8) and identified shared genetic architecture with AD, neuropsychiatric, and autoimmune traits.
Conclusions:
- Late-life memory exhibits significant heritability, with novel genetic variants and genes identified.
- Memory performance and decline share genetic links with AD, neuropsychiatric, and autoimmune conditions.
- These discoveries provide insights into the genetic architecture of cognitive aging.
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