Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 76, Issue 1, Pages 44-51Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nlw105
Keywords
Alzheimer disease; Tau protein; Soluble tau
Categories
Funding
- Alzheimer Association [NIRG 14-322078]
- Arizona Alzheimer's Consortium (National Institutes of Health/National Institute on Aging grant) [P30 AG19610]
- state of Arizona
- Barrow Neurological Foundation
- Barrow Neurological Institute
- University of Arizona, Phoenix
- National Institute of Neurological Disorders and Stroke [U24 NS072026]
- National Institute on Aging [P30 AG19610]
- Arizona Department of Health Services [211002]
- Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]
- Michael J. Fox Foundation for Parkinson's Research
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Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor. Our results suggest that the increase in NFT in AD is likely attributable to post-translational processes; the increase in CSF tau in AD patients is due to an accelerated carrier-based secretion. Moreover, cognitive dysfunction assessed by final Mini-Mental State Examination scores correlated with the secretion factor but not with the soluble tau.
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