Functional connectivity between the entorhinal and posterior cingulate cortices underpins navigation discrepancies in at-risk Alzheimer’s disease

Gillian Coughlan, Peter Zhukovsky, Vaisakh Puthusseryppady, Rachel Gillings, Anne-Marie Minihane, Donnie Cameron, Michael Hornberger

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Navigation processes that are selectively mediated by functional activity in the entorhinal cortex may be a marker of preclinical Alzheimer's disease (AD). Here, we tested if a short path integration paradigm can detect the strongest genetic-risk phenotype of AD in large sample of apolipoprotein E (APOE)-genotyped individuals. We also examined the associations between APOE-mediated navigation process, subjective cognitive decline, and rest-stating network connectivity. Navigation discrepancies classified 77% the APOE-genotyped cohort into their respective low-risk ε3ε3 and high-risk ε3ε4 categories. When connectivity strength between entorhinal and the posterior cingulate cortices (also a functional correlate of strongest APOE-dependant behavioral characteristics) was considered, this classification accuracy increased to 85%. Our findings present a whole picture of at-genetic-risk AD, including select impairment in path integration, self-report cognitive decline, and altered network activity that is reminiscent of the pathological spread of preclinical AD disease. These findings may have important implications for the early detection of AD.

Original languageEnglish
Pages (from-to)110-118
Number of pages9
JournalNeurobiology of Aging
Early online date19 Feb 2020
Publication statusPublished - Jun 2020


  • APOE genotype
  • Functional connectivity
  • Path integration
  • Preclinical Alzheimer's disease
  • Spatial navigation

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