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P3‐094: Three novel CSF assays expand a core panel of CSF biomarkers: BACE activity, oligomeric Aβ and homocysteine assessed in pathologically confirmed Alzheimer subjects within the Oxford project to investigate memory and aging (Optima) cohort
Author(s) -
Simon Adam J.,
Wu Guoxin,
Colussi Dennis,
Price Eric,
Barbacci Damon,
Getty Krista,
Shera David,
Seeburger Jeffrey,
Laterza Omar,
Tanaka Wesley,
Seabrook Guy,
Shearman Mark,
King Elizabeth,
Joachim Catharine,
Devanarayan Viswanath,
Smith David,
Sankaranarayanan Sethu
Publication year - 2008
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.2008.05.1658
Subject(s) - medicine , biomarker , homocysteine , alzheimer's disease , disease , oncology , pathology , chemistry , biochemistry
Background: A key goal within the Alzheimer’s disease (AD) research community is the early clinical detection and diagnosis of AD in patients who are at risk, or present with symptoms, of the disease. In addition to the standard clinical criteria, much effort in the field is aimed at identifying biochemical and imaging biomarkers. Methods: In a collaborative effort to discover early biomarkers of AD between OPTIMA and Merck Research Laboratories, we have expanded a panel of six previously validated and commercially available CSF biochemical assays for APP catabolites (A 40, A 42, sAPP , sAPP ) and tau (tTau, pTau-181). Three new assays were developed, optimized and analytically validated for (1) CSF BACE activity, (2) CSF oligomeric A , and (3) CSF Homocysteine (HCY) levels. These biochemical markers were measured in the CSF of pathologically confirmed AD (N 27-30) and clinically evaluated control cases (N 29). Results: Uni variate results exhibited an age-dependent increase in CSF BACE activity ( 1.0 pM/yr, p 0.05). In AD subjects, a modest but significant decline in age-adjusted CSF BACE activity was observed compared to controls (50% reduction, p 0.02). Regarding oligomeric A , in a commercially purchased sample set of human CSF, we found AD patients have 82 % higher oligomeric A levels than their age-matched non-demented controls (p 0.01). When oligomeric A was assessed in the post-mortem confirmed OPTIMA samples, there did not appear to be a significant difference between AD and CTL. One can’t be sure if there is an assay sensitivity issue or the demographics of the sample sets were different. Finally regarding CSF Homocysteine, we observed meaningful age dependence in CSF Homocysteine levels (slope 0.016 per year, p 0.0003). Differences between AD and CTL after age-adjustment are significant in females (11.2% greater in AD v CTL females, p 0.049). Conclusions: Taken together, these findings obtained from a post-mortem confirmed case analysis, enhance the putative value and use of specific CSF markers in support of the detection and diagnosis of Alzheimer’s disease. P3-095 LEVELS OF CSF BIOMARKERS PREDICT RATE OF COGNITIVE DECLINE IN INDIVIDUALS WITH VERY MILD DEMENTIA OF THE ALZHEIMER’S TYPE