Brain region‐specific amyloid plaque‐associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer's disease mice. Issue 1 (25th March 2020)

• Record Type: Journal Article
• Authors: Kaya, Ibrahim; Jennische, Eva; Lange, Stefan; Tarik Baykal, Ahmet; Malmberg, Per; Fletcher, John S.
• Is Part Of: Journal of neurochemistry. Volume 154:Issue 1(2020)
• Page Start: 84
• Page End: 98
• Publication Date: 2020-03-25
• Subjects: Alzheimer's disease -- amyloid plaques -- apolipoprotein E (APOE) -- MALDI Imaging Mass Spectrometry -- myelin lipids -- sulfatides; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14999
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: There is emerging evidence that amyloid beta (Aβ) aggregates forming neuritic plaques lead to impairment of the lipid‐rich myelin sheath and glia. 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; 5xFAD. 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 specific 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, implicated 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 deposition. This high‐spatial resolution matrix‐assisted laser desorption/ionization imaging mass spectrometry study in combination with (immuno) fluorescence staining of 5xFAD mouse brain provides new understanding of morphological, molecular and immune signatures of Aβ plaque pathology‐associated myelin lipid loss and myelin degeneration in a brain region‐specific manner. Read the Editorial Highlight for this article on page 7 . Abstract : We examined focal myelin lipid alterations and the disruption of the myelin sheath in amyloid plaques in 5XFAD mice. MALDI imaging mass spectrometry revealed Aβ plaque‐associated depletion of multiple myelin‐associated lipid species, prominently sulfatides. Double staining with fluoromyelin and amyloid‐specific antibody reveal amyloid plaque‐associated myelin sheath disruption on the edges of corpus callosum which is specifically correlated with plaque‐associated myelin lipid loss only in this region. Further, apolipoprotein (APOE) which is implicated with the depletion of sulfatides in the AD brain is deposited in all the Aβ plaques which suggest plaque‐associated APOE might mediate sulfatide depletion. Read the Editorial Highlight for this article on page 7 .