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 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. 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.
EricksonMAHartvigsonPEMorofujiYOwenJBButterfieldDABanksWA2012Lipopolysaccharide impairs amyloid beta efflux from brain: Altered vascular
sequestration, cerebrosinal fluid reabsorption, peripheral clearance and transporter
function at the blood-brain barrierJ Neuroinflammation9150
