title: Heparan sulfate accumulation with Abeta deposits in Alzheimer's disease and Tg2576 mice is contributed by glial cells.
abstract: Amyloid beta-peptide (Abeta) plaques, one of the major neuropathological lesions in Alzheimer's disease (AD), can be broadly subdivided into two morphological categories: neuritic and diffuse. Heparan sulfate (HS) and HS proteoglycans (HSPGs) are codeposits of multiple amyloidoses, including AD. Although HS has been considered a limiting factor in the initiation of amyloid deposition, the pathological implications of HS in Abeta deposits of AD remain unclear. In this study, immunohistochemistry combined with fluorescence and confocal microscopy was employed to gain deeper insight into the accumulation of HS with Abeta plaques in sporadic and familial AD. Here we demonstrate that HS preferentially accumulated around the Abeta40 dense cores of neuritic plaques, but was largely absent from diffuse Abeta42 plaques, suggesting that Abeta42 deposition may occur independently of HS. A codeposition pattern of HS with Abeta deposits in Tg2576 mice was also examined. We identified the membrane-bound HSPGs, glypican-1 (GPC1) and syndecan-3 (SDC3), in glial cells associated with Abeta deposits, proximal to sites of HS accumulation. In mouse primary glial cultures, we observed increased levels of GPC1 and SDC3 following Abeta stimulation. These results suggest that HS codeposits with Abeta40 in neuritic plaques and is mainly derived from glial cells.
authors.affiliation: Department of Public Health and Caring Sciences, Division of Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Callaghan
authors.forename: Elina
authors.initials: E
authors.lastname: Sandwall
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Guan
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Lars N G
authors.initials: LN
authors.lastname: Nilsson
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Hannu
authors.initials: H
authors.lastname: Kalimo
authors.forename: Ulf
authors.initials: U
authors.lastname: Lindahl
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D053673:Glypicans / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D053670:Syndecan-3 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D053673:Glypicans; D006497:Heparan Sulfate; D010446:Peptide Fragments; D053670:Syndecan-3; C078592:amyloid beta-protein (1-40)