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This study examined 1,000 healthy young adults (ages 18-35) to determine whether carriers of the APOE ε4 allele, the major genetic risk factor for Alzheimer's disease, show early differences in spatial navigation or cognitive abilities. Researchers found no significant differences in navigation performance or cognitive function between ε4 carriers and non-carriers, suggesting that APOE-related behavioral changes are minimal or absent in young adulthood. Exploratory findings indicated that ε2 carriers (a protective variant) showed some differences in navigation strategy and slightly better performance on certain cognitive tasks.
Why it matters
These findings suggest that spatial navigation tests may not be useful for identifying at-risk individuals decades before potential Alzheimer's onset, challenging the proposal to use such tasks for early detection. The results indicate that cognitive or behavioral markers of Alzheimer's risk in young APOE ε4 carriers are either non-existent or too subtle to detect with current methods.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Alzheimer’s disease (AD) causes progressive memory loss and disorientation. It is preceded by a prolonged preclinical phase marked by pathological changes in medial temporal lobe regions involved in spatial navigation. Spatial navigation tasks have been proposed for early AD detection, and altered navigation performance was reported in older carriers of the apolipoprotein E (APOE) {varepsilon}4 allele, the major genetic risk factor for sporadic AD. However, whether spatial navigation or other cognitive abilities are affected in younger {varepsilon}4 carriers remains unclear. Here, we genotyped 1000 healthy young adults (18-35 years) who completed the app-based navigation game "Sea Hero Quest" and several tasks assessing working memory, processing speed, executive functioning, and face recognition. {varepsilon}4 carriers ({varepsilon}3{varepsilon}4, N = 88) showed no significant differences from non-carriers ({varepsilon}3{varepsilon}3, N = 327) in spatial navigation or other cognitive abilities, supported by equivalence testing and Bayesian analyses. Exploratory findings suggested altered spatial navigation in {varepsilon}2 carriers ({varepsilon}2{varepsilon}2/{varepsilon}2{varepsilon}3/{varepsilon}2{varepsilon}4, Ns = 7/51/7) versus {varepsilon}3{varepsilon}3 controls, who stayed closer to environmental borders and showed better memory updating, face recognition, and processing speed. Therefore, APOE-related behavioural differences in young adults appear small at best, highlighting the need for paradigms sensitive to very subtle changes decades before potential dementia onset.