Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Perceptual discrimination of complex objects: Apolipoprotein E e4 gene-dose effects in mid-life.
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Lancaster Claire, Berens Sam, Daly Jessica, Rusted Jennifer, Bird Chris M
Аннотация
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.
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.