Unmasking selective path integration deficits in Alzheimer's disease risk carriers
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Unmasking selective path integration deficits in Alzheimer's disease risk carriers. / Bierbrauer, Anne; Kunz, Lukas; Gomes, Carlos A; Luhmann, Maike; Deuker, Lorena; Getzmann, Stephan; Wascher, Edmund; Gajewski, Patrick D; Hengstler, Jan G; Fernandez-Alvarez, Marina; Atienza, Mercedes; Cammisuli, Davide M; Bonatti, Francesco; Pruneti, Carlo; Percesepe, Antonio; Bellaali, Youssef; Hanseeuw, Bernard; Strange, Bryan A; Cantero, Jose L; Axmacher, Nikolai.
In: SCI ADV, Vol. 6, No. 35, eaba1394, 08.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Unmasking selective path integration deficits in Alzheimer's disease risk carriers
AU - Bierbrauer, Anne
AU - Kunz, Lukas
AU - Gomes, Carlos A
AU - Luhmann, Maike
AU - Deuker, Lorena
AU - Getzmann, Stephan
AU - Wascher, Edmund
AU - Gajewski, Patrick D
AU - Hengstler, Jan G
AU - Fernandez-Alvarez, Marina
AU - Atienza, Mercedes
AU - Cammisuli, Davide M
AU - Bonatti, Francesco
AU - Pruneti, Carlo
AU - Percesepe, Antonio
AU - Bellaali, Youssef
AU - Hanseeuw, Bernard
AU - Strange, Bryan A
AU - Cantero, Jose L
AU - Axmacher, Nikolai
N1 - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
PY - 2020/8
Y1 - 2020/8
N2 - Alzheimer's disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE ε4-carriers during a virtual navigation task. We report a selective impairment in APOE ε4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE ε4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset.
AB - Alzheimer's disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE ε4-carriers during a virtual navigation task. We report a selective impairment in APOE ε4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE ε4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset.
KW - Alzheimer Disease/genetics
KW - Apolipoprotein E4/genetics
KW - Entorhinal Cortex
KW - Heterozygote
KW - Humans
KW - Magnetic Resonance Imaging
KW - Young Adult
U2 - 10.1126/sciadv.aba1394
DO - 10.1126/sciadv.aba1394
M3 - SCORING: Journal article
C2 - 32923622
VL - 6
JO - SCI ADV
JF - SCI ADV
SN - 2375-2548
IS - 35
M1 - eaba1394
ER -