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Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes

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Ayberk, Kurt Mustafa

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Davies, David Ceri
Kidd, Michael
Duff, Karen
Rolph, S. C.
Jennings, Kevin H.
Howlett, David R.

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Academic Press Inc Elsevier Science

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Abstract

Mutations of amyloid precursor protein (APP) and presenilin-1 (PS1) lead to an increase in beta -amyloid (A beta) production. Despite the fact that a number of transgenic mice develop cerebral A beta plaques, few have been subjected to ultrastructural investigation and the sequence of events leading to A beta plaque formation is unclear. We therefore investigated the doubly transgenic (mutant APP(K670N,M671L)-mutant PS1(M146L)) mouse, which develops A beta deposits much earlier than singly transgenic littermates. Widespread A beta plaques with or without a distinct core were found in gray matter. A beta plaques were also present in white matter. Astrocytosis was greater around gray matter plaques than around white matter plaques. In some plaques, A beta cores were associated with cell profiles containing prominent endoplasmic reticulum and a homogenous cytoplasm that appeared to be neuronal. The morphology and location of other profiles indicated them to be microglia or oligodendrocytes. Some A beta fibrils appeared to lie within these profiles, but they may have been simply surrounded by the cell profile since the profile membrane was not always visible. Dark atrophic neurons, whose morphology suggested that they were apoptotic, were present around gray matter plaques. Cerebrovascular A beta deposition was also observed in the brains of A-PP/PS1 transgenic mice. Thus, the amyloid deposition and neuropathology observed in A-PP/PS1 mouse brain are similar to those in Alzheimer's disease and they appear to develop earlier and become more severe than in the other transgenic models currently available.

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Keywords

Alzheimers-disease, Senile plaques, A-beta, Diffuse plaques, Mouse models, Cells, Astrocytes, Immunoreactivity, A-beta-42(43), Angiopathy, Neurosciences & neurology

Citation

Kurt, M. A. vd. (2001). "Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes". Experimental Neurology, 171(1), 59-71.

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