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GM1 locates to mature amyloid structures implicating a prominent role for glycolipid-protein interactions in Alzheimer pathology.

Artikel i vetenskaplig tidskrift
Författare Wojciech Michno
Patrick M. Wehrli
Henrik Zetterberg
Kaj Blennow
Jörg Hanrieder
Publicerad i Biochimica et biophysica acta. Proteins and proteomics
Volym 1867
Nummer/häfte 5
Sidor 458-467
ISSN 1878-1454
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 458-467
Språk en
Länkar dx.doi.org/10.1016/j.bbapap.2018.09...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Analytisk kemi, Neurokemi

Sammanfattning

While the molecular mechanisms underlying Alzheimer's disease (AD) remain largely unknown, abnormal accumulation and deposition of beta amyloid (Aβ) peptides into plaques has been proposed as a critical pathological process driving disease progression. Over the last years, neuronal lipid species have been implicated in biological mechanisms underlying amyloid plaque pathology. While these processes comprise genetic features along with lipid signaling as well as direct chemical interaction of lipid species with Aβ mono- and oligomers, more efforts are needed to spatially delineate the exact lipid-Aβ plaque interactions in the brain. Chemical imaging using mass spectrometry (MS) allows to probe the spatial distribution of lipids and peptides in complex biological tissues comprehensively and at high molecular specificity. As different imaging mass spectrometry (IMS) modalities provide comprehensive molecular and spatial information, we here describe a multimodal ToF-SIMS- and MALDI-based IMS strategy for probing lipid and Aβ peptide changes in a transgenic mouse model of AD (tgAPPArcSwe). Both techniques identified a general AD-associated depletion of cortical sulfatides, while multimodal MALDI IMS revealed plaque specific lipid as well as Aβ peptide isoforms. In addition, MALDI IMS analysis revealed chemical features associated with morphological heterogeneity of individual Aβ deposits. Here, an altered GM1 to GM2/GM3 ganglioside metabolism was observed in the diffuse periphery of plaques but not in the core region. This was accompanied by an enrichment of Aβ1-40arc peptide at the core of these deposits. Finally, a localization of arachidonic acid (AA) conjugated phosphatidylinositols (PI) and their corresponding degradation product, lyso-phosphatidylinositols (LPI) to the periphery of Aβ plaques was observed, indicating site specific macrophage activation and ganglioside processing.

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