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Relationship between amyloid burden, cholinergic integrity, and cognitive function.

Li-Hua Lee1, Chia-Ju Chou1, Yao-Chia Shih2

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Journal of Alzheimer'S Disease : JAD
|December 22, 2025
PubMed
Summary
This summary is machine-generated.

Cholinergic white matter integrity is linked to amyloid buildup in early Alzheimer's disease, impacting cognitive function. This association is more evident in non-carriers of the apolipoprotein E4 gene.

Keywords:
Alzheimer's diseaseamyloid burdenapolipoprotein E4 carriercholinergic integritycognition

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Area of Science:

  • Neuroscience
  • Radiology
  • Gerontology

Background:

  • Amyloid accumulation and cholinergic white matter degeneration are hallmarks of early Alzheimer's disease (AD).
  • The precise relationship between amyloid burden and cholinergic pathway integrity in AD pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the association between amyloid accumulation, cholinergic white matter pathway integrity, and cognitive performance in early AD.
  • To explore how apolipoprotein E4 (APOE4) genotype influences these relationships.

Main Methods:

  • Cross-sectional study of 109 participants (37 controls, 72 early AD).
  • Neuropsychological testing (MMSE, CDR-SB, verbal fluency).
  • Diffusion tensor imaging (DTI) for cholinergic white matter integrity and amyloid positron emission tomography (PET) for amyloid burden.

Main Results:

  • Amyloid burden and cholinergic integrity were independently associated with cognitive performance in all participants.
  • In early AD, amyloid burden correlated with MMSE, and cholinergic integrity correlated with all cognitive measures.
  • Amyloid burden and cholinergic integrity were significantly correlated only in APOE4 non-carriers.

Conclusions:

  • Cholinergic white matter integrity, influenced by amyloid burden, may serve as a specific imaging biomarker for early Alzheimer's disease.
  • This association is particularly pronounced in individuals without the APOE4 gene variant.