APOE ε4 worsens hippocampal CA1 apical neuropil atrophy and episodic memory.

Abstract:

OBJECTIVES:Using high-resolution structural MRI, we endeavored to study the relationships among APOE ε4, hippocampal subfield and stratal anatomy, and episodic memory. METHODS:Using a cross-sectional design, we studied 11 patients with Alzheimer disease dementia, 14 patients with amnestic mild cognitive impairment, and 14 age-matched healthy controls with no group differences in APOE ε4 carrier status. Each subject underwent ultra-high-field 7.0-tesla MRI targeted to the hippocampus and neuropsychological assessment. RESULTS:We found a selective, dose-dependent association of APOE ε4 with greater thinning of the CA1 apical neuropil, or stratum radiatum/stratum lacunosum-moleculare (CA1-SRLM), a hippocampal subregion known to exhibit early vulnerability to neurofibrillary pathology in Alzheimer disease. The relationship between the ε4 allele and CA1-SRLM thinning persisted after controlling for dementia severity, and the size of other hippocampal subfields and the entorhinal cortex did not differ by APOE ε4 carrier status. Carriers also exhibited worse episodic memory function but similar performance in other cognitive domains compared with noncarriers. In a statistical mediation analysis, we found support for the hypothesis that CA1-SRLM thinning may link the APOE ε4 allele to its phenotypic effects on memory. CONCLUSIONS:The APOE ε4 allele segregated dose-dependently and selectively with CA1-SRLM thinning and worse episodic memory performance in a pool of older subjects across a cognitive spectrum. These findings highlight a possible role for this gene in influencing a critical hippocampal subregion and an associated symptomatic manifestation.

journal_name

Neurology

journal_title

Neurology

authors

Kerchner GA,Berdnik D,Shen JC,Bernstein JD,Fenesy MC,Deutsch GK,Wyss-Coray T,Rutt BK

doi

10.1212/WNL.0000000000000154

subject

Has Abstract

pub_date

2014-02-25 00:00:00

pages

691-7

issue

8

eissn

0028-3878

issn

1526-632X

pii

WNL.0000000000000154

journal_volume

82

pub_type

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