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Am J Neurodegener Dis 2012;1(1):99-106

Original Article
Tau is reduced in AD plasma and validation of employed ELISA methods

D Larry Sparks, Richard J Kryscio, Marwan N Sabbagh, Chuck Ziolkowski, Yushun Lin, Lisa M Sparks, Carolyn
Liebsack, Sherry Johnson-Traver

Roberts Laboratory for Neurodegenerative Disease Research Banner Sun Health Research Institute, Sun City, AZ,
USA; Department of Statistics, University of Kentucky, Lexington KY, USA; Cleo Roberts Clinical Research Center,
Banner Sun Health Research Institute, Sun City, AZ, USA.

Received April 26, 2012; accepted May 12, 2012; Epub May 15, 2012; published May 30, 2012

Abstract: Objective: Measure total tau levels in the circulation of living humans, validate the methods employed and
determine if there are consistent differences in total tau levels between normal controls and individuals with mild
cognitive impairment (MCI) and/or Alzheimer’s disease (AD). Methods:  Employing ELISA methods, validated by
Western bolts using three separate tau antibodies, we quantified total tau levels in serially collected serum and
plasma samples from individuals longitudinally evaluated for cognitive performance. Results: We identified substantial
levels of tau in human circulation using plasma, but not serum.  The measurement of authentic tau protein was verified
by Western blots using a C-terminal specific antibody, an N-terminal specific antibody and antibody used in the
commercially available ELISA kit.  We revealed a significant decrease in plasma levels of total tau among subjects with
MCI compared to cognitively normal controls, with a further highly significant reduction in AD patients compared to both
MCI and normal controls.  We also found a significant positive correlation between changing levels of plasma tau and
cognitive performance within the entire population and among AD patients. Conclusions:  The data suggest that
changes in circulating tau levels quantified in plasma samples, but not serum samples, may represent a viable
biomarker for tracking the progression of AD and the efficacy of medications in its treatment. (AJND1104007)

Keywords: Circulating tau levels, mild cognitive impairment, Alzheimer’s disease

Address all correspondence to:
Dr. D Larry Sparks
Roberts Laboratory for Neurodegenerative Disease Research
Banner Sun Health Research Institute
Sun City AZ 85351, USA.
Phone: (623) 876-5463; Fax (623) 876-5461
E-mail: Larry.Sparks@Bannerhealth.com