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

Functional connectivity between the entorhinal and posterior cingulate cortices underpins navigation discrepancies in at-risk Alzheimer's disease.
Functional connectivity between the entorhinal and posterior cingulate cortices underpins navigation discrepancies in at-risk Alzheimer's disease.
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.
0197-4580
110 - 118
Coughlan, G
d202a575-3974-4929-9010-b4d946578bba
Zhukovsky, P
22f2c5c6-7b13-41d8-8da5-8300b7a12784
Puthusseryppady, V
2c245ba1-16d3-4d03-a825-6b1d9b47bf77
Gillings, R
3da2a5e2-91f6-48e7-90a7-b53132045a9d
AM, Minihane
b9541773-aac8-4d70-ab1d-36fe58e42389
Cameron, D
c8951566-e497-4a81-b3bb-c0af745f12a6
Hornberger, M
a48c1c63-422a-4c11-9a51-c7be0aa3026d
Coughlan, G
d202a575-3974-4929-9010-b4d946578bba
Zhukovsky, P
22f2c5c6-7b13-41d8-8da5-8300b7a12784
Puthusseryppady, V
2c245ba1-16d3-4d03-a825-6b1d9b47bf77
Gillings, R
3da2a5e2-91f6-48e7-90a7-b53132045a9d
AM, Minihane
b9541773-aac8-4d70-ab1d-36fe58e42389
Cameron, D
c8951566-e497-4a81-b3bb-c0af745f12a6
Hornberger, M
a48c1c63-422a-4c11-9a51-c7be0aa3026d

Coughlan, G, Zhukovsky, P, Puthusseryppady, V, Gillings, R, AM, Minihane, Cameron, D and Hornberger, M (2020) Functional connectivity between the entorhinal and posterior cingulate cortices underpins navigation discrepancies in at-risk Alzheimer's disease. Neurobiology of Aging, 90, 110 - 118. (doi:10.1016/j.neurobiolaging.2020.02.007).

Record type: Article

Abstract

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.

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Published date: February 2020

Identifiers

Local EPrints ID: 505217
URI: http://eprints.soton.ac.uk/id/eprint/505217
ISSN: 0197-4580
PURE UUID: 07cd1d26-0c76-4ffa-9928-fcee4e3589ef
ORCID for M Hornberger: ORCID iD orcid.org/0000-0002-2214-3788

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Date deposited: 01 Oct 2025 16:53
Last modified: 02 Oct 2025 02:19

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Contributors

Author: G Coughlan
Author: P Zhukovsky
Author: V Puthusseryppady
Author: R Gillings
Author: Minihane AM
Author: D Cameron
Author: M Hornberger ORCID iD

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