Submit Manuscript  

Article Details


The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype

[ Vol. 17 , Issue. 7 ]

Author(s):

Matteo De Marco, Riccardo Manca, Janine Kirby, Guillaume M. Hautbergue, Daniel J. Blackburn, Stephen B. Wharton, Annalena Venneri* and Alzheimer’s Disease Neuroimaging Initiative   Pages 667 - 679 ( 13 )

Abstract:


<P>Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles. </P><P> Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-&#949;4 carriers and non-carriers. </P><P> 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 &#949;4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (A&#946;+/A&#946;-). Linear models were devised in each sub-cohort and for each APOE-&#949;4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps. </P><P> Results: PHS predicted memory and executive functioning in &#949;4&#949;3 MCI patients, memory in &#949;3&#949;3 MCI patients, and memory in &#949;4&#949;3 A&#946;+ participants. PHS also predicted volume in sensorimotor regions in &#949;3&#949;3 A&#946;+ participants. </P><P> Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-&#949;4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.</P>

Keywords:

Mild cognitive impairment, apolipoprotein, memory, executive function, polygenic traits, amyloid.

Affiliation:

Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX, Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX, Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX, Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX, Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX, Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX, Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX



Read Full-Text article