Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles. Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers. Methods: A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps. Results: PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants. Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.

The association between polygenic hazard and markers of Alzheimer’s disease following stratification for APOE genotype / De Marco, M.; Manca, R.; Kirby, J.; Hautbergue, G. M.; Blackburn, D. J.; Wharton, S. B.; Venneri, A.. - In: CURRENT ALZHEIMER RESEARCH. - ISSN 1567-2050. - 17:7(2020), pp. 667-679. [10.2174/1567205017666201006161800]

The association between polygenic hazard and markers of Alzheimer’s disease following stratification for APOE genotype

De Marco M.;Venneri A.
2020-01-01

Abstract

Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles. Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers. Methods: A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps. Results: PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants. Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.
2020
The association between polygenic hazard and markers of Alzheimer’s disease following stratification for APOE genotype / De Marco, M.; Manca, R.; Kirby, J.; Hautbergue, G. M.; Blackburn, D. J.; Wharton, S. B.; Venneri, A.. - In: CURRENT ALZHEIMER RESEARCH. - ISSN 1567-2050. - 17:7(2020), pp. 667-679. [10.2174/1567205017666201006161800]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2933267
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