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Longitudinal brain imaging in preclinical Alzheimer disease: impact of APOE ?4 genotype.


ABSTRACT: While prior work reliably demonstrates that the APOE ?4 allele has deleterious group level effects on Alzheimer disease pathology, the homogeneity of its influence across the lifespan and spatially in the brain remains unknown. Further it is unclear what combinations of factors at an individual level lead to observed group level effects of APOE genotype. To evaluate the impact of the APOE genotype on disease trajectories, we examined longitudinal MRI and PET imaging in a cohort of 497 cognitively normal middle and older aged participants. A whole-brain regional approach was used to evaluate the spatial effects of genotype on longitudinal change of amyloid-? pathology and cortical atrophy. Carriers of the ?4 allele had increased longitudinal accumulation of amyloid-? pathology diffusely through the cortex, but the emergence of this effect across the lifespan differed greatly by region (e.g. age 49 in precuneus, but 65 in the visual cortex) with the detrimental influence already being evident in some regions in middle age. This increased group level effect on accumulation was due to a greater proportion of ?4 carriers developing amyloid-? pathology, on average doing so at an earlier age, and having faster amyloid-? accumulation even after accounting for baseline amyloid-? levels. APOE ?4 carriers displayed faster rates of structural loss in primarily constrained to the medial temporal lobe structures at around 50 years, although this increase was modest and proportional to the elevated disease severity in APOE ?4 carriers. This work indicates that influence of the APOE gene on pathology can be detected starting in middle age.

SUBMITTER: Mishra S 

PROVIDER: S-EPMC5972633 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Longitudinal brain imaging in preclinical Alzheimer disease: impact of APOE ε4 genotype.

Mishra Shruti S   Blazey Tyler M TM   Holtzman David M DM   Cruchaga Carlos C   Su Yi Y   Morris John C JC   Benzinger Tammie L S TLS   Gordon Brian A BA  

Brain : a journal of neurology 20180601 6


While prior work reliably demonstrates that the APOE ɛ4 allele has deleterious group level effects on Alzheimer disease pathology, the homogeneity of its influence across the lifespan and spatially in the brain remains unknown. Further it is unclear what combinations of factors at an individual level lead to observed group level effects of APOE genotype. To evaluate the impact of the APOE genotype on disease trajectories, we examined longitudinal MRI and PET imaging in a cohort of 497 cognitivel  ...[more]

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