当前位置： SCI文献检索 > NEUROBIOLOGY OF DISEASE期刊下所有文献 > Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.

Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.

Abstract：

:Senile plaques composed mainly of beta-amyloid (Abeta) and neurofibrillary tangles principally composed of hyperphosphorylated tau are the major pathological features of Alzheimer's disease (AD). Despite the fact that increased expression of amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes in mice lead to increased Abeta deposition in plaquelike structures in the brain, little is known about the nature and distribution of tau in these mice. Therefore the relationship between Abeta and hyperphosphorylated tau was investigated in mice carrying mutant APP and mutant PS1 transgenes using both light (LM) and electron microscopy (EM) with immunocytochemistry. LM immunocytochemistry revealed cerebral Abeta deposits to be present from 8 weeks of age, whereas hyperphosphorylated tau was not detected until 24 weeks of age, when it appeared as punctate deposits in close association with the Abeta deposits in the cortex and hippocampus. However, dystrophic neurites were not as heavily immunolabeled as they are in AD brain. EM revealed that aggregations of straight filaments (10-12 nm wide) were present in some cellular processes at the periphery of Abeta plaques in 8-month-old APP/PS1 mice. In one such mouse, single filaments and paired filaments showing a helical configuration (50-55 nm half-period, 25 nm max. width) were present in a dark, atrophic hippocampal neuron. Immunogold labeling of APP/PS1 mouse brain revealed hyperphosphorylated tau epitopes in some dystrophic neurites from 24 weeks of age that were similar to those present in AD. These results suggest that hyperphosphorylated tau appears in APP/PS1 mouse brain after the onset of Abeta deposition and although it is associated with Abeta deposits, its distribution is not identical to that in AD.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Kurt MA,Davies DC,Kidd M,Duff K,Howlett DR

doi

10.1016/s0969-9961(03)00084-6

keywords:

subject

Has Abstract

pub_date

2003-10-01 00:00:00

pages

89-97

issue

eissn

0969-9961

issn

1095-953X

pii

S0969996103000846

journal_volume

pub_type

杂志文章

在线工具

Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.