Work

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

Year: 2001
Type: article
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.
Language: English
Subfield: Physiology
Field: Medicine
Open Access status: green
OpenAlex ID: W2001655937
FWCI: 2.761
Cites: 52
Cited by: 43
Related to: 10