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@ARTICLE{Fischer:276479,
      author       = {Fischer, Larissa and Molloy, Eóin N. and Pichet Binette,
                      Alexa and Vockert, Niklas and Marquardt, Jonas and Pacha
                      Pilar, Andrea and Kreißl, Michael and Remz, Jordana and
                      Tremblay-Mercier, Jennifer and Poirier, Judes and Rajah,
                      Maria Natasha and Villeneuve, Sylvia and Maass, Anne},
      collaboration = {Group, PREVENT-AD Research},
      title        = {{P}recuneus {A}ctivity during {R}etrieval {I}s {P}ositively
                      {A}ssociated with {A}myloid {B}urden in {C}ognitively
                      {N}ormal {O}lder {APOE}4 {C}arriers.},
      journal      = {The journal of neuroscience},
      volume       = {45},
      number       = {6},
      issn         = {0270-6474},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DZNE-2025-00298},
      pages        = {e1408242024},
      year         = {2025},
      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.},
      keywords     = {Humans / Female / Male / Apolipoprotein E4: genetics / Aged
                      / Parietal Lobe: metabolism / Parietal Lobe: diagnostic
                      imaging / Parietal Lobe: physiopathology / Middle Aged /
                      Amyloid beta-Peptides: metabolism / Magnetic Resonance
                      Imaging / Heterozygote / Positron-Emission Tomography /
                      Mental Recall: physiology / Longitudinal Studies /
                      Cognition: physiology / tau Proteins: metabolism / tau
                      Proteins: genetics / APOE4 (Other) / amyloid (Other) /
                      episodic memory retrieval (Other) / functional hyperactivity
                      (Other) / multimodal neuroimaging (Other) / precuneus
                      (Other) / Apolipoprotein E4 (NLM Chemicals) / Amyloid
                      beta-Peptides (NLM Chemicals) / tau Proteins (NLM
                      Chemicals)},
      cin          = {AG Maaß},
      ddc          = {610},
      cid          = {I:(DE-2719)1311001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39788739},
      doi          = {10.1523/JNEUROSCI.1408-24.2024},
      url          = {https://pub.dzne.de/record/276479},
}