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P4–356: Tau oligomers in CSF: A novel biomarker for the diagnosis and evaluation of treatment for Alzheimer's disease and tauopathies
Author(s) -
Sengupta Urmi,
Portelius Erik,
CastilloCarranza Diana,
Woltjer Randy,
Galasko Douglas,
Jackson George,
Blennow Kaj,
Kayed Rakez
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.08.190
Subject(s) - oligomer , biomarker , western blot , cerebrospinal fluid , tau protein , alzheimer's disease , antibody , chemistry , genetically modified mouse , tau pathology , disease , microbiology and biotechnology , pathology , medicine , transgene , biology , immunology , biochemistry , organic chemistry , gene
plasma samples from twoAlzheimer’s Disease Cooperative Studymulticenter studies: (1) Impact of donezepil and vitamin E in MCI patients and (2) impact of simvastatin in mild to moderate AD. We sought to determine factors that may influence plasma A b and whether levels of A b in plasma are associated with ApoE genotype and/or clinical and cognitive measures of AD progression. Methods: Levels of A b40 and 42 were detected with high throughput multiplex fluorescent bioassays from Innogenetics. An internal standard plasma sample was used to control for plate to plate variations and determine impact of storage time on A b. Longitudinal change in A b was assessed in the context of clinical, cognitive and laboratory data available from the clinical trial. Results: We found a significant effect of storage time on A b40 and 42. Although no longitudinal change was observed in either 18 month trial, we observed an impact of ApoE genotype on plasma A b42 in the MCI patient trial. Patients homozygous for ApoE4 had significantly less A b42 compared to individuals with no E4 alleles. Heterozygote individuals had levels in between those with no E4 alleles and those who were homozygous, but did not significantly differ from either group. Potentially due to low levels of A b40 and 42 of AD participants in the simvastatin trial, we did not observe a significant effect of ApoE genotype. We did, however, find a significant effect of simvastatin treatment; treated patients had significantly more A b42 than placebo controls. Conclusions: Our data suggest that plasmaAbmay be a viable biomarker of an interaction between ApoE genotype and change in plasma level of Ab42 in patients with MCI. With this data and the finding that simvastatin treatment resulted in a significant increase in levels of Ab42 in AD, our results suggest that detection of plasma Ab may prove to be a viable biomarker of AD.