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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Larissa Fischer1,2, Jenna N Adams2, Eóin N Molloy1,3

  • 1German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Functional connectivity (FC) changes in medial temporal lobe (MTL) and posteromedial cortex (PMC) are linked to Alzheimer's pathology and memory decline, especially in APOE4 carriers. Network changes differ between rest and task states.

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Area of Science:

  • Neuroscience
  • Cognitive Science
  • Medical Imaging

Background:

  • The medial temporal lobe (MTL) and posteromedial cortex (PMC) are crucial for episodic memory and are early sites of Alzheimer's disease (AD) pathology.
  • APOE4 genotype is a significant risk factor for AD, influencing pathology accumulation and cognitive decline.
  • Functional connectivity (FC) alterations within and between MTL and PMC may reflect compensatory or detrimental neural network changes in AD pathogenesis.

Purpose of the Study:

  • To investigate the relationship between longitudinal changes in functional connectivity (FC) within and between the MTL and PMC and Alzheimer's pathology burden.
  • To examine how these FC changes relate to cognitive performance, specifically delayed memory recall and object recognition.
  • To explore the moderating role of the APOE genotype in these associations.

Main Methods:

  • Longitudinal 3-Tesla fMRI data and cross-sectional amyloid-beta and tau PET imaging were analyzed from the PREVENT-AD cohort.
  • Changes in resting-state FC (RSFC) and task-based FC during object-location encoding were assessed within (ΔFCPMC, ΔFCMTL) and between (ΔFCMTL-PMC) these regions.
  • Multiple regression and linear mixed models were used to investigate associations between ΔFC, pathology, memory changes, and APOE genotype in 152 cognitively unimpaired older adults.

Main Results:

  • APOE genotype modulated the association between FC changes and pathology: declining RSFCPMC correlated with higher amyloid in APOE4 carriers, while increasing encoding-FCMTL correlated with higher tau in APOE4 carriers.
  • Increased encoding-FCPMC was associated with poorer memory performance (RBANS and object recognition) irrespective of APOE status.
  • Increased RSFCMTL-PMC was linked to improved RBANS performance, whereas increased encoding-FCMTL-PMC was linked to decreased object recognition.

Conclusions:

  • Longitudinal FC changes within and between MTL and PMC show APOE-dependent associations with AD pathology and memory performance.
  • Network alterations manifest differently during rest versus task conditions, highlighting the importance of dynamic FC assessments.
  • In APOE4 carriers, increased MTL connectivity during encoding relates to tau pathology, while decreased PMC connectivity during rest relates to amyloid, suggesting distinct pathological mechanisms in these regions.