TY  - JOUR
AU  - Fischer, Larissa
AU  - Molloy, Eóin N.
AU  - Pichet Binette, Alexa
AU  - Vockert, Niklas
AU  - Marquardt, Jonas
AU  - Pacha Pilar, Andrea
AU  - Kreißl, Michael
AU  - Remz, Jordana
AU  - Tremblay-Mercier, Jennifer
AU  - Poirier, Judes
AU  - Rajah, Maria Natasha
AU  - Villeneuve, Sylvia
AU  - Maass, Anne
TI  - Precuneus Activity during Retrieval Is Positively Associated with Amyloid Burden in Cognitively Normal Older APOE4 Carriers.
JO  - The journal of neuroscience
VL  - 45
IS  - 6
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.
M1  - DZNE-2025-00298
SP  - e1408242024
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Female
KW  - Male
KW  - Apolipoprotein E4: genetics
KW  - Aged
KW  - Parietal Lobe: metabolism
KW  - Parietal Lobe: diagnostic imaging
KW  - Parietal Lobe: physiopathology
KW  - Middle Aged
KW  - Amyloid beta-Peptides: metabolism
KW  - Magnetic Resonance Imaging
KW  - Heterozygote
KW  - Positron-Emission Tomography
KW  - Mental Recall: physiology
KW  - Longitudinal Studies
KW  - Cognition: physiology
KW  - tau Proteins: metabolism
KW  - tau Proteins: genetics
KW  - APOE4 (Other)
KW  - amyloid (Other)
KW  - episodic memory retrieval (Other)
KW  - functional hyperactivity (Other)
KW  - multimodal neuroimaging (Other)
KW  - precuneus (Other)
KW  - Apolipoprotein E4 (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39788739
DO  - DOI:10.1523/JNEUROSCI.1408-24.2024
UR  - https://pub.dzne.de/record/276479
ER  -