Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 9, Pages 6364-6369Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.092136199
Keywords
-
Categories
Funding
- NIA NIH HHS [AG15383] Funding Source: Medline
- NINDS NIH HHS [NS39080, R01 NS039080] Funding Source: Medline
Ask authors/readers for more resources
Senile plaques and neurofibrillary tangles, the two hallmark lesions of Alzheimer's disease, are the results of the pathological deposition of proteins normally present throughout the brain. Senile plaques are extracellular deposits of fibrillar beta-amyloid peptide (Abeta); neurofibrillary tangles represent intracellular bundles of self-assembled hyperphosphorylated tau proteins. Although these two lesions are often present in the same brain areas, a mechanistic link between them has yet to be established. In the present study, we analyzed whether tau plays a key role in fibrillar A,B-induced neurite degeneration in central neurons. Cultured hippocampal neurons obtained from wild-type, tau knockout, and human tau transgenic mice were treated with fibrillar Abeta. Morphological analysis indicated that neurons expressing either mouse or human tau proteins degenerated in the presence of Abeta. On the other hand, tau-depleted neurons showed no signs of degeneration in the presence of Abeta. These results provide direct evidence supporting a key role for tau in the mechanisms leading to Abeta-induced neurodegeneration in the central nervous system. In addition, the analysis of the composition of the cytoskeleton of tau-depleted neurons suggested that the formation of more dynamic microtubules might confer resistance to Abeta-mediated neurodegeneration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available