title: Amylin alters human brain pericyte viability and NG2 expression.
abstract: Amylin, a pancreatic β-cell-derived peptide hormone, forms inclusions in brain microvessels of patients with dementia who have been diagnosed with type 2 diabetes and Alzheimer's disease. The cellular localization of these inclusions and the consequences thereof are not yet known. Using immunohistochemical staining of hippocampus and parahippocampal cortex from patients with Alzheimer's disease and non-demented controls, we show that amylin cell inclusions are found in pericytes. The number of amylin cell inclusions did not differ between patients with Alzheimer's disease and controls, but amylin-containing pericytes displayed nuclear changes associated with cell death and reduced expression of the pericyte marker neuron-glial antigen 2. The impact of amylin on pericyte viability was further demonstrated in in vitro studies, which showed that pericyte death increased in presence of fibril- and oligomer amylin. Furthermore, oligomer amylin increased caspase 3/7 activity, reduced lysate neuron-glial antigen 2 levels and impaired autophagy. Our findings contribute to increased understanding of how aggregated amylin affects brain vasculature and highlight amylin as a potential factor involved in microvascular pathology in dementia progression.
authors.affiliation: 1 Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Schultz
authors.affiliation: 1 Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Byman
authors.affiliation: 2 Unit for Molecular Metabolism, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Fex
authors.affiliation: 1 Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Wennström
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000941:Antigens / Q000096:biosynthesis*; D001343:Autophagy / Q000187:drug effects; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D058228:Islet Amyloid Polypeptide / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020286:Pericytes / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D058228:Islet Amyloid Polypeptide; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: Alzheimer’s disease; cell death mechanisms; diabetes; hippocampus; pericytes