Brain Abeta amyloidosis in APPsw mice induces accumulation of presenilin-1 and tau.
APPsw transgenic mice (Tg2576) overproducing mutant amyloid beta protein precursor (betaAPP) show substantial brain Abeta 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 alpha-synuclein and postsynaptic protein drebrin were also absent in the amyloid cores. betaAPP 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 Abeta amyloidosis in the induction of secondary pathological steps leading to mental disturbance in Alzheimer's disease.
Tomidokoro
Y
Y
Department of Neurology, Gunma University School of Medicine, 3-39-22 Showamachi, Maebashi, Gunma 371-8511, Japan. tomidoko@med.gunma-u.ac.jp
Harigaya
Y
Y
Matsubara
E
E
Ikeda
M
M
Kawarabayashi
T
T
Shirao
T
T
Ishiguro
K
K
Okamoto
K
K
Younkin
S G
SG
Shoji
M
M
D000544:Alzheimer Disease / Q000378:metabolism; D017772:Amyloid Neuropathies / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020739:Brain Diseases, Metabolic, Inborn / Q000378:metabolism*; D004195:Disease Models, Animal; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016501:Neurites / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D053764:Presenilin-1; D016875:tau Proteins / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1; D016875:tau Proteins