Perceptual discrimination of complex objects: Apolipoprotein E e4 gene-dose effects in mid-life

Abstract

INTRODUCTION: Complex perceptual discrimination is supported by tau-vulnerable regions of the medial temporal lobe (MTL); notably the perirhinal cortex. This research tests whether there is a gene-dose effect of apolipoprotein E (APOE) e4 on perceptual discrimination in mid-life. METHODS: Three hundred and thirteen adults (45–65 years; grouped by APOE e4 gene-dose (142 APOE33, 135 APOE34, 36 APOE44)) completed a Greebles “odd-one-out” task. RESULTS: APOE44 carriers were significantly less accurate in their perceptual judgments than APOE33 and APOE34 individuals. There was a significant Age x APOE e4 gene-dose interaction in response speed, with the slope of age-related slowing increasing stepwise with the number of e4 alleles carried. Estimates suggest high-risk individuals are quicker than the APOE33 control group until age 54, but slower thereafter. DISCUSSION: Perceptual disadvantages specific to APOE44 individuals suggest this high-risk group show compromised MTL function by mid-life, potentially through accelerated tau-aggregation. Task performance in APOE34 carriers is relatively preserved in mid-life. Highlights: APOE44 carriers show impaired perceptual discrimination in mid-age. APOE34 carriers show preserved perceptual discrimination in mid-age. Age-related slowing of perceptual judgments increases with APOE e4 gene-dose. Perceptual discrimination tasks may be a valuable early marker of AD risk.