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P3‐417: Endoplasmic reticulum stress in Alzheimer's disease
Author(s) -
Scheper Wiep,
Chafekar Sidhartha M.,
López-Cavanillas María,
Zwart Rob,
Hoozemans Jeroen J.M.,
Baas Frank
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1988
Subject(s) - unfolded protein response , endoplasmic reticulum , downregulation and upregulation , microbiology and biotechnology , golgi apparatus , blot , western blot , chemistry , biology , biochemistry , gene
HS with high affinity and this relationship is possibly mutually protective. As part of the immune/inflammatory response, neuritic plaques are surrounded by activated astrocytes and microglia, many of which perish at the plaque site forming the glial scar. Results from animal models of brain injury have demonstrated glial upregualtion of the membrane bound HSPGs, glypican (GPC) and syndecan (SDC), which have been implicated in regulation of axon regeneration. Here we discuss the possibility that HS accumulation, with specific plaque types and A species, is derived from A -stimulated glial cells presenting with elevated levels of membrane bound GPC1 and SDC3. Methods: Brain sections from sporadic AD, Swedish mutation AD, Presenilin-1 (PS1)9 AD and Tg2576 mice were immunostained for A , HS, HSPGs, and glial markers. Astrocytes and microglia from neonatal C57BL mice were separated; stimulated with aggregated A 42; and GPC1 and SDC3 levels for each cell type was analysed by Western immunoblotting. Results: GPC1 and SDC3 immunostaining overlaps with astrocytes around the neuritic, A 40/ HS-positive plaques of sporadic AD and Swedish mutation AD. Conversely, GPC1, SDC3 and HS are largely absent from the diffuse A 42 rich plaques found in Swedish mutation AD and PS19 AD, which incite little to no astrocyte response. Immunostaining in Tg2576 mice showed that glial cells in contact with A /HS-positive deposits, expressed GPC1 and SDC3. Purified astrocytes and microglia, stimulated with aggregated A 42, presented with elevated levels of GPC1 and SDC3. Conclusions: Here we describe the preferential accumulation of HS with A 40-positive plaques and its relative absence from A 42-rich diffuse deposits in AD. This discrimination coincided with the presence or absence of astrocytes, which overlapped with the HSPGs, GPC1 and SDC3. Finally, cultures of purified astrocytes and microglia revealed elevated levels of both HSPGs, in response to A stimulation.