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. 2012;1(1):99-106.
Epub 2012 May 15.

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

D Larry Sparks  1 , Richard J Kryscio, Marwan N Sabbagh, Chuck Ziolkowski, Yushun Lin, Lisa M Sparks, Carolyn Liebsack, Sherry Johnson-Traver
Affiliations

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

D Larry Sparks et al. Am J Neurodegener Dis. 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.

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

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Figures

Figure 1
Figure 1
Western blot of standards and plasma samples immunostained with the total-tau antibody employed in the total-tau quantification ELISA kits produced by Invitrogen. Molecular weight standards are in lane 1, tau isoform standards are in lane 2, and authentic human 441 tau is seen in lane 4. No sample (blanks) was added to lanes 3, 5, 6, 8, 10, 12 and 14. A plasma sample - after stripping IgG - from an Alzheimer’s patient was applied to lane 7, from an individual with MCI to lane 9, from a control subject to lane 11, from a rabbit fed control diet to lane 13 and from a rabbit fed a 1% cholesterol diet to lane 15.
Figure 2
Figure 2
Western blot of standards and plasma samples immunostained with tau-12 antibody (C-terminal) suppliedby Dr. Lester Binder. Molecular weight standards are in lane 1, tau isoform standards are in lane 2, and authentichuman 441 tau is seen in lane 3. No sample (blanks) was added to lanes 4, 6, 8, 10, 12 and 14. A plasma sample - after stripping IgG - from two separate AD patients are seen in lanes 5 and 7, from two separate individuals withMCI are in lanes 9 and 11, and from two separate age-matched control are in lanes 13 and 15.
See this image and copyright information in PMC

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