Diagnostic utility of APOE, soluble CD40, CD40L, and Aβ1-40 levels in plasma in Alzheimer's disease

A continuous inflammatory state is associated with Alzheimer's disease (AD) evidenced by an increase in proinflammatory cytokines around beta-amyloid (A beta) deposits. In addition, functional loss of CD40L is shown to result in diminished Amyloid precursor proton (APP) processing and microglial activation, supporting a prominent role of CD40-CD40L in AD etiology. We therefore hypothesize that a peripheral increase in A beta may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis. We measured plasma A beta, sCD40 and sCD40L levels in 73 AD patients and compared to 102 controls matched on general demographics. We demonstrated that A beta(1-40), levels of sCD40 and sCD40L are increased in AD and declining MMSE scores correlated with increasing sCD40L, which in turn, correlated positively with A beta(1-42). We then combined sCD40, sCD40L, A beta and APOE and found that this biomarker panel has high sensitivity and specificity (>90%) as a predictor of clinical AD diagnosis. Given the imminent availability of potentially disease modifying therapies for AD, a great need exists for peripheral diagnostic markers of AD. Thus, we present preliminary evidence for potential usefulness for combination of plasma sCD40, sCD40L along with A beta(1-40) and APOE epsilon 4 in improving the clinical diagnosis of AD. (C) 2008 Elsevier Ltd. All rights reserved.