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Autosomal dominant Alzheimer's disease (ADAD) mutation carriers show early visual memory deficits before clinical symptoms emerge. The APOE ε4 gene variant did not appear to worsen memory performance in this preclinical ADAD study.

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Area of Science:

  • Neuroscience
  • Genetics
  • Cognitive Psychology

Background:

  • Autosomal dominant Alzheimer's disease (ADAD) offers insights into early Alzheimer's disease (AD) cognitive changes.
  • The role of APOE ε4 in sporadic AD is established, but its impact on ADAD cognitive phenotypes is unclear.

Purpose of the Study:

  • Investigate the effect of APOE ε4 co-occurrence with APPV717I or PSEN1A431E mutations on preclinical ADAD cognitive function.
  • Determine if specific mutations and APOE ε4 influence cognitive performance in individuals at risk for ADAD.

Main Methods:

  • Genetic analysis (APPV717I/PSEN1A431E mutations, APOE genotyping) and neuropsychological evaluation (CERAD-MX) were performed on 81 Mexican-mestizo individuals.
  • Participants were categorized into mutation carriers (C) and non-carriers (NC), and further stratified by APOE ε4 status (ε4+/ε4-).
  • Cognitive performance was assessed using normalized z-scores across 12 CERAD-MX tasks, with group differences analyzed using non-parametric tests.

Main Results:

  • Mutation carriers (C) demonstrated significantly lower performance in visual memory tasks (Constructional Praxis-Recall, Rey-Osterrieth Complex Figure-Recall) compared to non-carriers (NC).
  • Within mutation carriers, those without the APOE ε4 allele (Cε4-) showed poorer Rey-Osterrieth Complex Figure-Recall performance compared to non-carriers without the APOE ε4 allele (NCε4-).

Conclusions:

  • Early visual memory impairment is detectable in the preclinical stage of ADAD.
  • The APOE ε4 allele did not show a detrimental effect on memory performance in this ADAD cohort.
  • Further research with larger sample sizes is needed to confirm findings and explore other cognitive domains and influencing factors like APOE ancestry.