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Amyloid and tau pathologies together, not alone, drive nucleus basalis of Meynert (Ch4) atrophy in cognitively unimpaired individuals. Amyloid presence is necessary for tau to significantly impact Ch4 volume.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Radiology

Background:

  • The cholinergic basal forebrain (BF) system, specifically the nucleus basalis of Meynert (Ch4), shows early vulnerability in Alzheimer's disease (AD).
  • Mechanisms and onset of Ch4 atrophy in relation to AD pathologies remain unclear.
  • Investigating early-stage Ch4 degeneration in cognitively unimpaired (CU) individuals provides insight into AD pathogenesis.

Purpose of the Study:

  • To investigate the relationship between Ch4 volume and amyloid-beta (Aβ) and tau pathologies in CU individuals.
  • To understand the role of Aβ and tau in Ch4 atrophy during the earliest stages of AD-related changes.

Main Methods:

  • Cross-sectional study of 335 CU individuals from the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort.
  • Utilized PET imaging for Aβ and tau, alongside MRI for Ch4 volumetric measures.
  • Quantified tau burden in the mesial-temporal (ME) region and assessed Aβ and tau positivity thresholds.

Main Results:

  • Ch4 volume correlated with Aβ levels but not ME tau burden in CU individuals.
  • In CU individuals with ME tau positivity, Ch4 volume was associated with Aβ levels, with tau mediating 58.1% of the effect.
  • Ch4 volume correlated with ME tau levels only when Aβ pathology was present.

Conclusions:

  • The combined presence of amyloid and tau pathologies is linked to reduced Ch4 volume.
  • Ch4 is not vulnerable to mesial-temporal tau pathology in the absence of detectable amyloid pathology.
  • Amyloid pathology may facilitate a more direct role for tau pathology in Ch4 degeneration.