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.
journal_name
Proc Natl Acad Sci U S Aauthors
Bi X,Yong AP,Zhou J,Ribak CE,Lynch Gdoi
10.1073/pnas.151253098keywords:
subject
Has Abstractpub_date
2001-07-17 00:00:00pages
8832-7issue
15eissn
0027-8424issn
1091-6490pii
151253098journal_volume
98pub_type
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