Secretion of human tau fragments resembling CSF-tau in Alzheimer's disease is modulated by the presence of the exon 2 insert.
Abnormal tau cleavage is prominent in the neurofibrillary degeneration characteristic of Alzheimer's disease (AD) and related tauopathies. We recently showed that cleaved human tau is secreted by specific mechanisms when overexpressed. Here we examined the effect of expressing N-terminal and full length tau constructs in transiently and stably transfected neuronal lines. We show that secreted tau exhibits a cleavage pattern similar to CSF-tau from human AD patients and that tau secretion is specifically inhibited by the presence of the exon 2 insert. These results suggest that tau secretion may play a hitherto unsuspected role in AD and related tauopathies.
Kim
Wonhee
W
Center for Cellular Neuroscience and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.
Lee
Sangmook
S
Hall
Garth F
GF
D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000627:therapeutic use; D004304:Dosage Forms; D004333:Drug Administration Routes; D005091:Exons; D006801:Humans; D051379:Mice; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D024801:Tauopathies / Q000188:drug therapy / Q000235:genetics
D003598:Cytoskeletal Proteins; D004304:Dosage Forms