Brain region-specific amyloid plaque-associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer's disease mice
Journal article, 2020

There is emerging evidence that amyloid beta (A beta) 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 A beta(42) peptide-rich plaque deposition in the brain parenchyma. Matrix-assisted laser desorption/ionization imaging mass spectrometry of coronal brain tissue sections revealed focal A beta 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 A beta plaques which suggest apolipoprotein E might mediate sulfatide depletion as a consequence of an immune response to A beta 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 A beta plaque pathology-associated myelin lipid loss and myelin degeneration in a brain region-specific manner.

apolipoprotein E (APOE)

myelin lipids

amyloid plaques

Alzheimer's disease

sulfatides

MALDI Imaging Mass Spectrometry

Author

I. Kaya

University of Gothenburg

Eva Jennische

University of Gothenburg

Stefan Lange

University of Gothenburg

Ahmet Tarik Baykal

Acibadem University

Per Malmberg

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

John S. Fletcher

University of Gothenburg

Journal of Neurochemistry

0022-3042 (ISSN) 1471-4159 (eISSN)

Vol. 154 1 84-98

Subject Categories

Neurosciences

Chemical Sciences

DOI

10.1111/jnc.14999

PubMed

32141089

More information

Latest update

7/9/2020 6