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.
Keywords: Mild cognitive impairment, apolipoprotein, memory, executive function, polygenic traits, amyloid.
[http://dx.doi.org/10.2174/156720501604190424114752] [PMID: 31104627]
[http://dx.doi.org/10.1186/alzrt155] [PMID: 23302773]
[http://dx.doi.org/10.2217/bmm-2017-0388] [PMID: 29896987]
[http://dx.doi.org/10.1038/ng.2802] [PMID: 24162737]
[http://dx.doi.org/10.1111/nan.12101] [PMID: 24443964]
[http://dx.doi.org/10.1016/S1474-4422(16)00127-7] [PMID: 27302364]
[http://dx.doi.org/10.1007/s00429-014-0738-4] [PMID: 24578178]
[http://dx.doi.org/10.1038/npp.2015.30] [PMID: 25630570]
[http://dx.doi.org/10.1007/s12035-015-9638-8] [PMID: 26742530]
[http://dx.doi.org/10.1016/j.tig.2019.02.005] [PMID: 30922659]
[http://dx.doi.org/10.1002/acn3.716] [PMID: 30911569]
[http://dx.doi.org/10.1176/appi.ajp.2017.17050529] [PMID: 29495896]
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.12.022] [PMID: 29358118]
[http://dx.doi.org/10.1093/brain/awy327] [PMID: 30689776]
[http://dx.doi.org/10.1016/j.biopsych.2012.04.009] [PMID: 22592056]
[http://dx.doi.org/10.1016/j.jalz.2014.12.008] [PMID: 25916564]
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.02.016] [PMID: 27103528]
[http://dx.doi.org/10.1371/journal.pmed.1002258] [PMID: 28323831]
[http://dx.doi.org/10.3389/fnins.2018.00260] [PMID: 29760643]
[http://dx.doi.org/10.1007/s00401-017-1789-4] [PMID: 29177679]
[http://dx.doi.org/10.1016/j.jalz.2018.02.009] [PMID: 29601787]
[http://dx.doi.org/10.1002/jmri.21049] [PMID: 18302232]
[http://dx.doi.org/10.1006/nimg.2000.0582] [PMID: 10860804]
[http://dx.doi.org/10.1016/j.neuroimage.2014.09.034] [PMID: 25255942]
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606]
[http://dx.doi.org/10.1016/j.jalz.2018.01.010] [PMID: 29499171]
[http://dx.doi.org/10.1007/s11682-012-9186-z] [PMID: 22782295]
[http://dx.doi.org/10.1007/s11682-012-9176-1] [PMID: 22644789]
[PMID: 10912591]
[http://dx.doi.org/10.1093/cercor/bhw157] [PMID: 27230218]
[http://dx.doi.org/10.1093/gerona/60.10.1319] [PMID: 16282567]
[http://dx.doi.org/10.1097/WAD.0b013e31818877b5] [PMID: 19266700]
[http://dx.doi.org/10.1001/jamaneurol.2016.3474] [PMID: 27842173]
[http://dx.doi.org/10.1007/s11682-017-9818-4] [PMID: 29396739]
[http://dx.doi.org/10.1212/WNL.0000000000005415] [PMID: 29592889]
[http://dx.doi.org/10.1002/ana.24999] [PMID: 28727176]
[PMID: 30569081]
[http://dx.doi.org/10.1016/S1474-4422(19)30435-1] [PMID: 31986256]
[http://dx.doi.org/ 10.1093/braincomms/fcz047]
[PMID: 19504470]