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P1–037: Protease nexin–2/amyloid ß–protein precursor regulates the extent of cerebral thrombosis
Author(s) -
Van Nostrand William E.,
Davis Judianne,
Miao Jianting,
Previti Mary Lou,
Romanov Galina,
Ziegler Kelly,
Xu Feng
Publication year - 2006
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.2006.05.412
Subject(s) - platelet , serpin , amyloid precursor protein , platelet activation , genetically modified mouse , biology , alzheimer's disease , chemistry , pathology , medicine , transgene , biochemistry , immunology , gene , disease
ods: APPDutch mice (overexpressing hAPP E693Q) were crossed with transgenic PS45 (overexpressing hPS1 G384A), BACE54 (overexpressing hBACE1), or APP23 mice (overexpressing hAPP K670N/M671L). All mice were analyzed at 22-24 months of age by immunohistochemistry and Western blotting. Results: APPDutch/PS45 mice develop severe A 42-driven parenchymal amyloidosis with very little vascular amyloid. APPDutch/BACE54 mice reveal more vascular amyloid deposits compared to APPDutch mice and furthermore exhibit parenchymal amyloid. APPDutch/APP23 mice show more vascular amyloid and, interestingly, less parenchymal amyloid compared to APP23 mice. Amyloid deposits in these double-transgenic mice mainly contain A 40 that in turn consists of both mutated and wild-type A , respectively. Conclusions: A 42 and A 40 drive amyloid pathology in different cerebral compartments, i.e. parenchyma versus vasculature. Abundant A 42 provokes the formation of parenchymal amyloid, while a specific increase in A 40 favors the development of vascular amyloid and appears to reduce parenchymal amyloid formation.