Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 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 (Abeta) 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 Abeta may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis. We measured plasma Abeta, sCD40 and sCD40L levels in 73 AD patients and compared to 102 controls matched on general demographics. We demonstrated that Abeta(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 Abeta(1-42). We then combined sCD40, sCD40L, Abeta 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 Abeta(1-40) and APOE epsilon4 in improving the clinical diagnosis of AD.
Ait-ghezala
Ghania
G
Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. gaitghezala@rfdn.org
Abdullah
Laila
L
Volmar
Claude-Henry
CH
Paris
Daniel
D
Luis
Cheryl A
CA
Quadros
Amita
A
Mouzon
Benoit
B
Mullan
Myles A
MA
Keegan
Andrew P
AP
Parrish
Julia
J
Crawford
Fiona C
FC
Mathura
Venkatarajan S
VS
Mullan
Michael J
MJ
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019013:CD40 Antigens / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D005260:Female; D006801:Humans; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000097:blood; D012680:Sensitivity and Specificity
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D019013:CD40 Antigens; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D023201:CD40 Ligand