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[P2–248]: CARDIOVASCULAR RISK AND MILD COGNITIVE IMPAIRMENT PROGRESSING TO ALZHEIMER'S DISEASE
Author(s) -
Lopez Roa Lina Maria,
Conde Giancarlos,
Miranda Beatriz,
Garcia Yasmina,
Agredo Zuñiga Ricardo Antonio,
Maza Victor Pardo
Publication year - 2017
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.2017.06.900
Subject(s) - medicine , overweight , risk factor , montreal cognitive assessment , disease , cognitive decline , diabetes mellitus , logistic regression , gerontology , type 2 diabetes , population , dementia , alzheimer's disease , obesity , physical therapy , environmental health , endocrinology
specific antibodies was used for immunization. IP-MS analyses of tau were done to confirm the specificity of the mAb’s. ELISA or Simoa assays were developed using recombinant Tau fragments as calibrators. Assay characteristics (accuracy, precision, limit of detection) were evaluated. Finally, for each fragment, pilot studies to evaluate the diagnostic potential for AD was evaluated, as well as the correlation to total tau. Results:The IP-MS experiments identified three novel cleavage sites on tau in CSF. Immunization resulted in several mAb’s which were end-specific for the novel fragments. Specificity of mAb’s was confirmed and ELISA or Simoa assays were demonstrated to be able to quantify the tau fragments in CSF with assays ranging from low pg/mL to high ng/mL. Preliminary results suggest that the tau fragments may represent different pools of tau and that some of the fragments may have diagnostic information. Conclusions:We have demonstrated that antibody based enrichment of tau followed by high resolution MS analyses allows for the identification of novel fragments of tau in CSF. Pilot studies confirm the feasibility of analysing these fragments both in patients with AD and controls. The initial clinical validation demonstrates a potential diagnostic value for some of the fragments. The results presented will add to our current understanding on tau processing and tau pathologies.