Inflammation Combined with Ischemia Produces Myelin Injury and Plaque-Like Aggregates of Myelin, Amyloid-β and AβPP in Adult Rat Brain

Journal of Alzheimer's Disease : JAD
Xinhua ZhanFrank R Sharp

Abstract

Ischemia, white matter injury, and Alzheimer's disease (AD) pathologies often co-exist in aging brain. How one condition predisposes to, interacts with, or perhaps causes the others remains unclear. To better understand the link between ischemia, white matter injury, and AD, adult rats were administered lipopolysaccharide (LPS) to serve as an inflammatory stimulus, and 24 h later subjected to 20-min focal cerebral ischemia (IS) followed by 30-min hypoxia (H). Myelin and axonal damage, as well as amyloid-β (Aβ) and amyloid-β protein precursor (AβPP) deposition were examined by Western blot and immunocytochemistry following LPS/IS/H. Findings were compared to the 5XFAD mouse AD brain. Myelin/axonal injury was observed bilaterally in cortex following LPS/IS/H, along with an increase in IL-1, granzyme B, and LPS. AβPP deposition was present in ischemic striatum in regions of myelin loss. Aβ(1-42) and AβPP were deposited in small foci in ischemic cortex that co-localized with myelin aggregates. In the 5XFAD mouse AD model, cortical amyloid plaques also co-localized with myelin aggregates. LPS/IS/H produce myelin injury and plaque-like aggregates of myelin. AβPP and Aβ co-localize with these myelin aggregates.

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Citations

Apr 12, 2016·Frontiers in Neurology·Jordi A Matías-GuiuJorge Matías-Guiu
Feb 15, 2018·Journal of Alzheimer's Disease : JAD·Niraj Kumar JhaPravir Kumar
Apr 25, 2018·Frontiers in Immunology·Olga N Kokiko-Cochran, Jonathan P Godbout
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Apr 15, 2021·GeroScience·Behnam Sabayan, Rudi G J Westendorp

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