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Updated: Jan 14, 2026
Full- versus Sub-Regional Quantification of Amyloid-Beta Load on Mouse Brain Sections
Published on: May 19, 2022
The impact of amyloid beta burden on white matter dysfunction and associated transcriptomic signatures in cognitively
Ziyun Li1,2, Yuxiao Sun1,2, Ting Li1,2
1State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal University Beijing China.
Introduction:
Amyloid beta (Aβ), a hallmark of early Alzheimer's disease (AD), disrupts white matter (WM) microstructure, but its spatial patterns and transcriptomic links in cognitively normal individuals remain underexplored.
Methods:
We compared the WM microstructure between Aβ-positive (Aβ+) and Aβ-negative (Aβ-) individuals at the cognitively normal stage. We investigated the relationship between the fibers and the cortical and subcortical regions to which they are connected, as well as the underlying gene expression.
Results:
WM damage observed in Aβ+ individuals was characterized across eight fiber tracts, even prior to the evidence of atrophy and during the cognitive normal stage. This damage is primarily associated with cortical Aβ accumulation and may be linked to genes that regulate oligodendrocyte function and myelination.
Discussion:
Cortical Aβ-related WM changes precede gray matter atrophy in preclinical AD, highlighting their potential as early biomarkers. Oligodendrocyte dysfunction and myelination pathways may underlie Aβ-driven WM vulnerability, offering targets for intervention.
Highlights:
WM microstructural changes precede gray matter atrophy in preclinical AD.Aβ-driven WM damage persists even after adjusting for age.WM microstructural damage is primarily linked to cortical Aβ burden in cognitively normal individuals.Oligodendrocytes and myelin underlie the vulnerability of WM-related to Aβ.
Insights
Amyloid beta (Aβ) accumulation damages white matter (WM) in cognitively normal individuals before gray matter atrophy occurs in preclinical Alzheimer's disease (AD). This WM damage may involve oligodendrocyte dysfunction and myelination pathways.
Area of Science:
- Neuroscience
- Neuropathology
- Biomarker Discovery
Background:
- Amyloid beta (Aβ) is a key marker in early Alzheimer's disease (AD).
- Aβ disrupts white matter (WM) microstructure.
- Spatial patterns and genetic links of Aβ-related WM changes in cognitively normal individuals are not well understood.
Purpose of the Study:
- To compare WM microstructure in cognitively normal individuals with and without Aβ.
- To investigate the relationship between WM fiber tracts and connected brain regions.
- To explore the underlying gene expression related to Aβ-driven WM changes.
Main Methods:
- Comparison of WM microstructure between Aβ-positive and Aβ-negative cognitively normal individuals.
- Analysis of fiber tract connections to cortical and subcortical regions.
- Investigation of gene expression linked to WM integrity.
Main Results:
- WM damage was observed in eight fiber tracts in Aβ-positive individuals, preceding atrophy.
- This damage correlated with cortical Aβ accumulation.
- Potential links to genes regulating oligodendrocyte function and myelination were identified.
Conclusions:
- Cortical Aβ-related WM changes precede gray matter atrophy in preclinical AD, serving as potential early biomarkers.
- Oligodendrocyte dysfunction and myelination pathways may explain Aβ-driven WM vulnerability.
- These findings suggest potential therapeutic targets for intervention.
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