Age-dependent changes in brain, CSF, and plasma amyloid β protein in the Tg2576 transgenic mouse model of Alzheimer's disease

Takeshi Kawarabayashi, Linda H. Younkin, Takaomi C. Saido, Mikio Shoji, Karen Hsiao Ashe, Steven G. Younkin

Research output: Contribution to journalArticlepeer-review

844 Scopus citations

Abstract

The accumulation of amyloid β protein (Aβ) in the Tg2576 mouse model of Alzheimer's disease (AD) was evaluated by ELISA, immunoblotting, and immunocytochemistry. Changes in Aβ begin at 6-7 months as SDS-insoluble forms of Aβ42 and Aβ40 that require formic acid for solubilization appear. From 6 to 10 months, these insoluble forms increase exponentially. As insoluble Aβ appears, SDS-soluble Aβ decreases slightly, suggesting that it may be converting to an insoluble form. Our data indicate that it is full-length unmodified Aβ that accumulates initially in Tg2576 brain. SDS-resistant Aβ oligomers and most Aβ species that are N-terminally truncated or modified develop only in older Tg2576 mice, in which they are present at levels far lower than in human AD brain. Between 6 and 10 months, when SDS-insoluble Aβ42 and Aβ40 are easily detected in every animal, histopathology is minimal because only isolated Aβ cores can be identified. By 12 months, diffuse plaques are evident. From 12 to 23 months, diffuse plaques, neuritic plaques with amyloid cores, and biochemically extracted Aβ42 and Aβ40 increase to levels like those observed in AD brains. Coincident with the marked deposition of Aβ in brain, there is a decrease in CSF Aβ and a substantial, highly significant decrease in plasma Aβ. If a similar decline occurs in human plasma, it is possible that measurement of plasma Aβ may be useful as a premorbid biomarker for AD.

Original languageEnglish (US)
Pages (from-to)372-381
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number2
DOIs
StatePublished - Jan 15 2001

Keywords

  • Alzheimer's disease
  • Amyloid β protein
  • Cerebrospinal fluid
  • Neurodegeneration
  • Plasma
  • Tg2576 transgenic animal model

ASJC Scopus subject areas

  • Neuroscience(all)

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