Inflammation combined with ischemia produces myelin injury and plaque-like aggregates of myelin, amyloid-β and AβPP in adult rat brain

Xinhua Zhan, Christopher Cox, Bradley Ander, Da Liu, Boryana Stamova, Lee-Way Jin, Glen C. Jickling, Frank R Sharp

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: 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. Objectives: 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). Methods: 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. Results: Myelin/axonal injurywas 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. Aβ1-42 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. Conclusions: LPS/IS/H produce myelin injury and plaque-like aggregates of myelin. AβPP and Aβ co-localize with these myelin aggregates.

Original languageEnglish (US)
Pages (from-to)507-523
Number of pages17
JournalJournal of Alzheimer's Disease
Volume46
Issue number2
DOIs
StatePublished - 2015

Keywords

  • Alzheimer's disease
  • amyloid plaques
  • amyloid-β
  • amyloid-β protein precursor
  • hypoxia
  • lipopolysaccharide
  • myelin
  • myelin basic protein

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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