Brain Aβ amyloidosis in APPsw mice induces accumulation of presenilin-1 and tau

Yasushi Tomidokoro, Yasuo Harigaya, Etsuro Matsubara, Masaki Ikeda, Takeshi Kawarabayashi, Tomoaki Shirao, Koichi Ishiguro, Koichi Okamoto, Steven G. Younkin, Mikio Shoji

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)500-506
Number of pages7
JournalJournal of Pathology
Volume194
Issue number4
DOIs
StatePublished - Jan 1 2001

Keywords

  • Alzheimer's disease
  • Brain Aβ amyloidosis
  • Drebrin
  • Hyperphosphorylated tau
  • Presenilin-1
  • Transgenic mice
  • α-synuclein
  • βAPP

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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