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

INTRODUCTIONComplex perceptual discrimination is supported by tau-vulnerable regions of the medial temporal lobe; notably the perirhinal cortex. This research tests whether there is a gene-dose effect of Apolipoprotein e4 on perceptual discrimination in mid-life. METHODS313 adults (45-65 years; grouped by APOE e4 gene-dose (142 APOE33, 135 APOE34, 36 APOE44)) completed a Greebles odd-one-out task. RESULTSAPOE44 carriers were significantly less accurate in their perceptual judgements 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. DISCUSSIONPerceptual 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 across the studied age range. Research in ContextO_LISystematic review: A review of the literature (e.g., PubMed; Google Scholar databases) revealed perceptual discrimination is impaired in the mild to moderate stages of Alzheimers Disease. No prior study, however, tests for an effect of APOE e4 gene-dose in healthy adulthood. C_LIO_LIInterpretation: Homozygous carriers of an APOE e4 genetic risk variant show perceptual disadvantages in mid-life. This may possibly reflect compromised MTL-function in this group, consistent with the theory perceptual discrimination will be vulnerable to early transentorhinal tau-accumulation. There is limited evidence of impairment in individuals carrying one copy of APOE e4 in mid-life. C_LIO_LIFuture directions: Whether transentorhinal and hippocampal tau mediates the relationship between APOE e4 gene-dose and perceptual discrimination remains to be established. Future research may also explore the utility of perceptual discrimination tasks in clinical trials targeting the preclinical stages of Alzheimers Disease. C_LI