Journal Article

DZNE-2025-00298

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Precuneus Activity during Retrieval Is Positively Associated with Amyloid Burden in Cognitively Normal Older APOE4 Carriers.

Fischer, L. (First author)DZNE* ; Molloy, E. N.DZNE* ; Pichet Binette, A. ; Vockert, N.DZNE* ; Marquardt, J.DZNE* ; Pacha Pilar, A.Extern* ; Kreißl, M.Extern* ; Remz, J. ; Tremblay-Mercier, J. ; Poirier, J. ; Rajah, M. N. ; Villeneuve, S. ; Group, P. R. (Collaboration Author) ; Maass, A. (First author)DZNE*

2025
Soc. Washington, DC

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Please use a persistent id in citations: doi:10.1523/JNEUROSCI.1408-24.2024

Abstract: The precuneus is a site of early amyloid-beta (Aβ) accumulation. Previous cross-sectional studies reported increased precuneus fMRI activity in older adults with mild cognitive deficits or elevated Aβ. However, longitudinal studies in early Alzheimer's disease (AD) are lacking and the relationship to the Apolipoprotein-E (APOE) genotype is unclear. Investigating the PREVENT-AD dataset, we assessed how baseline and longitudinal precuneus activity during successful memory retrieval relates to future Aβ and tau burden and change in memory performance. We further studied the moderation by APOE4 genotype. We included 165 older adults (age, 62.8 ± 4.4 years; 113 female; 66 APOE4 carriers) who were cognitively normal at baseline with a family history of AD. All participants performed task-fMRI at baseline and underwent 18F-flortaucipir-PET and 18F-NAV4694-Aβ-PET on average 5 years later. We found that higher baseline activity and greater longitudinal increase in precuneus activity were associated with higher Aβ burden in APOE4 carriers but not noncarriers. We observed no effects of precuneus activity on tau burden. Finally, APOE4 noncarriers with low baseline precuneus activity exhibited better longitudinal performance in an independent memory test compared with (1) noncarriers with higher baseline activity and (2) APOE4 carriers. Our findings suggest that higher task-related precuneus activity during memory retrieval at baseline and over time are associated with greater Aβ burden in cognitively normal APOE4 carriers. Our results further indicate that the absence of 'hyperactivation' and the absence of the APOE4 allele is related with better future cognitive outcomes in cognitively normal older adults at risk for AD.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Male (MeSH) ; Apolipoprotein E4: genetics (MeSH) ; Aged (MeSH) ; Parietal Lobe: metabolism (MeSH) ; Parietal Lobe: diagnostic imaging (MeSH) ; Parietal Lobe: physiopathology (MeSH) ; Middle Aged (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Heterozygote (MeSH) ; Positron-Emission Tomography (MeSH) ; Mental Recall: physiology (MeSH) ; Longitudinal Studies (MeSH) ; Cognition: physiology (MeSH) ; tau Proteins: metabolism (MeSH) ; tau Proteins: genetics (MeSH) ; APOE4 ; amyloid ; episodic memory retrieval ; functional hyperactivity ; multimodal neuroimaging ; precuneus ; Apolipoprotein E4 ; Amyloid beta-Peptides ; tau Proteins

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Contributing Institute(s):

1. Multimodal Neuroimaging (AG Maaß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Software Fischer, L.DZNE*
Software: precuneus_retrieval_hyperactivation_publication
Zenodo (2025) [10.5281/zenodo.16103671]2025   Files BibTeX | EndNote: XML, Text | RIS

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