Diagnostic utility of APOE, soluble CD40, CD40L, and Aβ_1–40 levels in plasma in Alzheimer’s disease

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• 作者：Ghania Ait-ghezala ; Laila Abdullah ; Claude-Henry Volmar ; Daniel Paris ; Cheryl A. Luis ; Amita Quadros ; Benoit Mouzon ; Myles A. Mullan ; Andrew P. Keegan ; Julia Parrish ; Fiona C. Crawford ; Venkatarajan S
• 关键词：CD40 ; Alzheimer ; ApoE ; Amyloid beta ; Diagnostic
• 刊名：Cytokine
• 出版年：2008
• 出版时间：November 2008
• 年：2008
• 卷：44
• 期：2
• 页码：283-287
• 全文大小：190 K

文摘

A continuous inflammatory state is associated with Alzheimer’s disease (AD) evidenced by an increase in proinflammatory cytokines around beta-amyloid (Aβ) 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 Aβ may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis. We measured plasma Aβ, sCD40 and sCD40L levels in 73 AD patients and compared to 102 controls matched on general demographics. We demonstrated that Aβ_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 Aβ_1–42. We then combined sCD40, sCD40L, Aβ 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 Aβ₁₋₄₀ and APOE ε4 in improving the clinical diagnosis of AD.