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

Area of Science:

• Neuroscience
• Genetics
• Cognitive Psychology

Background:

• Complex perceptual discrimination relies on medial temporal lobe (MTL) regions, particularly the perirhinal cortex.
• The apolipoprotein E (APOE) e4 allele is a significant genetic risk factor for Alzheimer's disease (AD).

Purpose of the Study:

• To investigate the gene-dose effect of APOE e4 on perceptual discrimination abilities in mid-life adults.
• To determine if APOE e4 influences MTL function and cognitive performance in middle age.

Main Methods:

• Three hundred thirteen adults aged 45-65 were grouped by APOE e4 gene-dose: APOE33 (n=142), APOE34 (n=135), and APOE44 (n=36).
• Participants completed a Greebles "odd-one-out" perceptual discrimination task.

Main Results:

• APOE44 carriers demonstrated significantly lower accuracy in perceptual judgments compared to APOE33 and APOE34 individuals.
• A significant interaction between age and APOE e4 gene-dose was observed in response speed, with age-related slowing increasing with higher e4 allele counts.
• Estimates indicate that APOE44 carriers are faster than APOE33 individuals until age 54, after which they become slower.

Conclusions:

• Impaired perceptual discrimination in APOE44 carriers suggests compromised MTL function by mid-life, potentially linked to accelerated tau-aggregation.
• Perceptual discrimination tasks may serve as early indicators of Alzheimer's disease risk.
• APOE34 carriers exhibit preserved perceptual discrimination in mid-life, indicating relatively protected MTL function.