Rapid induction of intraneuronal neurofibrillary tangles in apolipoprotein E-deficient mice.

Abstract:

:Cultured hippocampal slices prepared from apolipoprotein E-deficient mice were exposed to an inhibitor of cathepsins B and L and then processed for immunocytochemistry using antibodies against human paired helical filaments. Dense, AT8-immunopositive deposits were found in the subiculum, stratum oriens of hippocampal field CA1, and the hilus of the dentate gyrus. This distribution agrees with that described for tangles in Alzheimer's disease. The appearance of the labeled structures fell into categories that correspond to previously proposed stages in the progression of intraneuronal neurofibrillary tangles in human hippocampus. Electron microscopic analyses confirmed that microtubule disruption and twisted bundles of filaments were present in neurons in the affected areas. These results support the hypothesis that partial lysosomal dysfunction is a contributor to Alzheimer's disease and suggest a simple model for studying an important component of the disease.

authors

Bi X,Yong AP,Zhou J,Ribak CE,Lynch G

doi

10.1073/pnas.151253098

keywords:

subject

Has Abstract

pub_date

2001-07-17 00:00:00

pages

8832-7

issue

15

eissn

0027-8424

issn

1091-6490

pii

151253098

journal_volume

98

pub_type

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