Open AccessHeparan Sulfate Accumulation with Aβ Deposits in Alzheimer's Disease and Tg2576 Mice is Contributed by Glial Cells
Author(s) -
O'Callaghan Paul,
Sandwall Elina,
Li JinPing,
Yu Hong,
Ravid Rivka,
Guan ZhiZhong,
Van Kuppevelt Toin H.,
Nilsson Lars N. G.,
Ingelsson Martin,
Hyman Bradley T.,
Kalimo Hannu,
Lindahl Ulf,
Lannfelt Lars,
Zhang Xiao
Publication year - 2008
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2008.00152.x
Subject(s) - senile plaques , heparan sulfate , pathology , alzheimer's disease , amyloid (mycology) , chemistry , immunohistochemistry , syndecan 1 , microbiology and biotechnology , biology , glycosaminoglycan , biochemistry , disease , cell , medicine
Amyloid β‐peptide (Aβ) 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 Aβ 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 Aβ plaques in sporadic and familial AD. Here we demonstrate that HS preferentially accumulated around the Aβ40 dense cores of neuritic plaques, but was largely absent from diffuse Aβ42 plaques, suggesting that Aβ42 deposition may occur independently of HS. A codeposition pattern of HS with Aβ 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 Aβ deposits, proximal to sites of HS accumulation. In mouse primary glial cultures, we observed increased levels of GPC1 and SDC3 following Aβ stimulation. These results suggest that HS codeposits with Aβ40 in neuritic plaques and is mainly derived from glial cells.