Precuneus Activity during Retrieval Is Positively Associated with Amyloid Burden in Cognitively Normal Older APOE4 Carriers
(2025) In Journal of Neuroscience 45(6).- 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... (More)
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.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2025-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloid, APOE4, episodic memory retrieval, functional hyperactivity, multimodal neuroimaging, precuneus
- in
- Journal of Neuroscience
- volume
- 45
- issue
- 6
- article number
- e1408242024
- publisher
- Society for Neuroscience
- external identifiers
-
- pmid:39788739
- scopus:85217222808
- ISSN
- 0270-6474
- DOI
- 10.1523/JNEUROSCI.1408-24.2024
- language
- English
- LU publication?
- yes
- id
- c6f23546-b4f6-4b03-a6d4-6c19b83ff41c
- date added to LUP
- 2025-04-02 13:11:51
- date last changed
- 2025-07-09 21:04:33
@article{c6f23546-b4f6-4b03-a6d4-6c19b83ff41c,
abstract = {{<p>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 <sup>18</sup>F-flortaucipir-PET and <sup>18</sup>F-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.</p>}},
author = {{Fischer, Larissa and Molloy, Eóin N. and Binette, Alexa Pichet and Vockert, Niklas and Marquardt, Jonas and Pilar, Andrea Pacha and Kreissl, Michael C. and Remz, Jordana and Tremblay-Mercier, Jennifer and Poirier, Judes and Rajah, Maria Natasha and Villeneuve, Sylvia and Maass, Anne}},
issn = {{0270-6474}},
keywords = {{amyloid; APOE4; episodic memory retrieval; functional hyperactivity; multimodal neuroimaging; precuneus}},
language = {{eng}},
number = {{6}},
publisher = {{Society for Neuroscience}},
series = {{Journal of Neuroscience}},
title = {{Precuneus Activity during Retrieval Is Positively Associated with Amyloid Burden in Cognitively Normal Older APOE4 Carriers}},
url = {{http://dx.doi.org/10.1523/JNEUROSCI.1408-24.2024}},
doi = {{10.1523/JNEUROSCI.1408-24.2024}},
volume = {{45}},
year = {{2025}},
}