Brain region ‐specific amyloid plaque‐associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer’s disease mice

In this study, we examined focal myelin lipid alterations and the disruption of the myelin sheath associated with amyloid plaques in a widely used familial Alzheimer's disease (AD) mouse model; 5xF AD. This AD mouse model has Aβ42 peptide ‐rich plaque deposition in the brain parenchyma. Matrix‐assisted laser desorption/ionization imaging mass spectrometry of coronal brain tissue sections revealed focal Aβ plaque‐associated depletion of multiple myelin‐associated lipid species including sulfatides, galactosylceramides, and sp ecific plasmalogen phopshatidylethanolamines in the hippocampus, cortex, and on the edges of corpus callosum. Certain phosphatidylcholines abundant in myelin were also depleted in amyloid plaques on the edges of corpus callosum. Further, lysophosphatidylethanolamines and lysophosphatidylcholines, im plicated in neuroinflammation, were found to accumulate in amyloid plaques. Double staining of the consecutive sections with fluoromyelin and amyloid‐specific antibody revealed amyloid plaque‐associated myelin sheath disruption on the edges of the corpus callosum which is specifically correlated with plaque‐associated myelin lipid loss only in this region. Further, apolipoprotein E, which is implicated in depletion of sulfatides in AD brain, is deposited in all the Aβ plaques which suggest apolipoprotein E might mediate sulfatide depletion as a consequence of an immune response to Aβ d eposition. This high‐spatial resolution matrix‐assist...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research