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Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
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Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia

Emilie T Reas1, Donald J Hagler2, Joshua M Kuperman2

  • 1Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.

Journal of Alzheimer'S Disease : JAD
|December 5, 2019
PubMed
Abstract

Insights

Brain amyloid-beta (Aβ) is linked to widespread microstructural changes. Regional brain microstructure, not Aβ, predicts cognitive decline in Alzheimer's disease, offering insights beyond amyloid pathology.

Area of Science:

  • Neuroimaging
  • Alzheimer's Disease Biomarkers
  • Cognitive Neuroscience

Background:

  • Alzheimer's disease (AD) diagnosis relies on biomarkers like amyloid-beta (Aβ) and brain changes.
  • The distinct and combined impacts of Aβ and brain microstructure on cognitive decline remain incompletely understood.

Purpose of the Study:

  • To investigate the relationship between Aβ, brain microstructure, and cognitive decline in individuals with mild cognitive impairment (MCI) and AD dementia.
  • To determine if brain microstructure mediates the effects of Aβ on cognitive decline.

Main Methods:

  • Utilized restriction spectrum imaging (RSI) and cerebrospinal fluid (CSF) Aβ measurements.
  • Calculated neurite density (ND) and isotropic free water diffusion (IF) in specific brain regions and fiber tracts.
  • Analyzed longitudinal cognitive data from healthy controls, MCI, and mild-to-moderate AD dementia patients.

Main Results:

  • Reduced ND and increased IF in specific fiber tracts and medial temporal lobe regions predicted cognitive impairment and decline.
  • Microstructural measures predicted cognitive outcomes independently of Aβ levels.
  • Amyloid-beta (Aβ) showed correlations with whole-brain microstructure, not regional measures.

Conclusions:

  • Regional microstructural integrity, rather than amyloid-beta (Aβ), is a key predictor of cognitive decline in AD.
  • Brain microstructure alterations may explain cognitive decline independent of amyloid pathology.
  • Microstructural imaging offers valuable insights into neural injury contributing to cognitive decline in AD.
Keywords:
AgingAlzheimer’s diseaseamyloidcognitive declinedementiadiffusion imagingmagnetic resonance imagingmemorymild cognitive impairment

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