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Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.
- Source :
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Alzheimer's Research & Therapy . 12/12/2023, Vol. 15 Issue 1, p1-10. 10p. - Publication Year :
- 2023
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Abstract
- Background: Genome-wide association studies demonstrate that Alzheimer's disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility. Methods: Here, we recruited sixteen clinically asymptomatic individuals (mean age 67; range 58–76) with either extremely low / high AD-PRS (defined as at least 2 standard deviations from the wider sample mean (N = 4504; NEFFECTIVE = 90)) with comparable age sex and education level. We assessed group differences in autobiographical memory and T1-weighted structural neuroimaging features. Results: We observed marked reductions in autobiographical recollection (Cohen's d = − 1.66; PFDR = 0.014) and midline structure (cingulate) thickness (Cohen's d = − 1.55, PFDR = 0.05), with no difference in hippocampal volume (P > 0.3). We further confirm the negative association between AD-PRS and cingulate thickness in a larger study with a comparable age (N = 31,966, β = − 0.002, P = 0.011), supporting the validity of our approach. Conclusions: These observations conform with multiple streams of prior evidence suggesting alterations in cingulate structures may occur in individuals with higher AD genetic risk. We were able to use a genetically informed research design strategy that significantly improved the efficiency and power of the study. Thus, we further demonstrate that the recall-by-genotype of AD-PRS from wider samples is a promising approach for the detection, assessment, and intervention in specific individuals with increased AD genetic risk. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17589193
- Volume :
- 15
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Alzheimer's Research & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 174179312
- Full Text :
- https://doi.org/10.1186/s13195-023-01362-y