Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.
Alzheimer’s disease
Neuroimaging
Polygenic risk score
Recall-by-genotype
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
12 Dec 2023
12 Dec 2023
Historique:
received:
21
08
2023
accepted:
29
11
2023
medline:
13
12
2023
pubmed:
13
12
2023
entrez:
13
12
2023
Statut:
epublish
Résumé
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. 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; N We observed marked reductions in autobiographical recollection (Cohen's d = - 1.66; P 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.
Sections du résumé
BACKGROUND
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
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; N
RESULTS
RESULTS
We observed marked reductions in autobiographical recollection (Cohen's d = - 1.66; P
CONCLUSIONS
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.
Identifiants
pubmed: 38087383
doi: 10.1186/s13195-023-01362-y
pii: 10.1186/s13195-023-01362-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
213Subventions
Organisme : Medical Research Council
ID : MC_PC_17189
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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