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Brain Aβ amyloidosis in APPsw mice induces accumulation of presenilin‐1 and tau
Author(s) -
Tomidokoro Yasushi,
Harigaya Yasuo,
Matsubara Etsuro,
Ikeda Masaki,
Kawarabayashi Takeshi,
Shirao Tomoaki,
Ishiguro Koichi,
Okamoto Koichi,
Younkin Steven G.,
Shoji Mikio
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.897
Subject(s) - neurite , amyloid (mycology) , presenilin , amyloidosis , nissl body , congo red , tau protein , biology , pathology , genetically modified mouse , amyloid precursor protein , bace1 as , senile plaques , alzheimer's disease , neuroscience , chemistry , transgene , biochemistry , medicine , staining , disease , gene , in vitro , organic chemistry , adsorption
Abstract APPsw transgenic mice (Tg2576) overproducing mutant amyloid β protein precursor (βAPP) show substantial brain Aβ amyloidosis and behavioural abnormalities. To clarify the subsequent abnormalities, the disappearance of neurons and synapses and dystrophic neurite formation with accumulated proteins including hyperphosphorylated tau were examined. Tg2576 demonstrated substantial giant core plaques and diffuse plaques. The number of neurons was significantly decreased in the areas containing the amyloid cores compared with all other areas and corresponding areas in non‐transgenic littermates in sections visualized by Nissl plus Congo red double staining ( p <0.001). The presynaptic protein α‐synuclein and postsynaptic protein drebrin were also absent in the amyloid cores. βAPP and presenilin‐1 were accumulated in dystrophic neurites in and around the core plaques. Tau phosphorylated at five independent sites was detected in the dystrophic neurites in the amyloid cores. Thus, the giant core plaques replaced normal brain tissues and were associated with subsequent pathological features such as dystrophic neurites and the appearance of hyperphosphorylated tau. These findings suggest a potential role for brain Aβ amyloidosis in the induction of secondary pathological steps leading to mental disturbance in Alzheimer's disease. Copyright © 2001 John Wiley & Sons, Ltd.