Delineating Amyloid Plaque Associated Neuronal Sphingolipids in Transgenic Alzheimer's Disease Mice (tgArcSwe) Using MALDI Imaging Mass Spectrometry
Artikel i vetenskaplig tidskrift, 2017

The major pathological hallmarks of Alzheimer's disease (AD) are the progressive aggregation and accumulation of beta-amyloid (A beta) and hyperphosphorylated tau protein into neurotoxic deposits. A beta aggregation has been suggested as the critical early inducer, driving the disease progression. However, the factors that promote neurotoxic A beta aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides, and proteins in biological tissue sections. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)-based imaging was used on transgenic Alzheimer's disease mouse (tgArcSwe) brain tissue to investigate the sphingolipid microenvironment of individual A beta plaques and elucidate plaque-associated sphingolipid alterations. Multivariate data analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their lipid chemical profile. This approach revealed sphingolipid species that distinctly located to cortical and hippocampal deposits, whose A beta identity was further verified using fluorescent amyloid staining and immunohistochemistry. Subsequent multivariate statistical analysis of the spectral data revealed significant localization of gangliosides and ceramides species to A beta positive plaques, which was accompanied by distinct local reduction of sulfatides. These plaque-associated changes in sphingolipid levels implicate a functional role of sphingolipid metabolism in A beta plaque pathology and AD pathogenesis. Taken together, the presented data highlight the potential of imaging mass spectrometry as a powerful approach for probing A beta plaque-associated lipid changes underlying AD pathology.

amyloid-beta plaque pathology

sublimation

Neurosciences

ceramide

Biochemistry & Molecular Biology

MALDI imaging mass spectrometry

cholesterol

Alzheimer's disease

sphingolipids

membrane-lipids

animal-models

gm1

beta-protein

Pharmacology & Pharmacy

accumulation

gangliosides

pathogenesis

& Neurology

Författare

I. Kaya

Sahlgrenska akademin

D. Brinet

Sahlgrenska akademin

Göteborgs universitet

W. Michno

Sahlgrenska akademin

S. Syvanen

Uppsala universitet

D. Sehlin

Uppsala universitet

Henrik Zetterberg

Sahlgrenska akademin

UCL Institute of Neurology

Sahlgrenska universitetssjukhuset

Kaj Blennow

Sahlgrenska akademin

Sahlgrenska universitetssjukhuset

Jörg Hanrieder

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Analytisk kemi

ACS Chemical Neuroscience

1948-7193 (ISSN)

Vol. 8 2 347-355

Ämneskategorier

Kemiteknik

DOI

10.1021/acschemneuro.6b00391

Mer information

Senast uppdaterat

2018-04-17