Potential Utility of Soluble p3-Alcadeinα Plasma Levels as a Biomarker for Sporadic Alzheimer's Disease

Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins (alpha, beta, gamma) that share identical localization and function to the amyloid-beta protein precursor (A beta PP) in the brain. Alcs are proteolyzed in neurons through successive cleavages via secretases, resulting in non-aggregative p3-Alc, where p3 corresponds to the A beta PP-fragment. We found p3-Alc alpha detected in human plasma reflected the pathological process of amyloid-beta accumulation in Alzheimer's disease (AD) patients and therefore investigated the utility of p3-Alc alpha as a plasma biomarker in AD. We measured p3-Alc alpha plasma levels in 83 sporadic-AD, 18 mild cognitive impaired (MCI), and 24 control subjects using the sandwich-ELISA system. Pooled samples with previously published data (171 AD and 45 controls) were also analyzed. The plasma p3-Alc alpha concentrations in patients with AD and MCI were significantly higher compared with control subjects (224.7 +/- 40.4, 223.3 +/- 53.9, and 189.1 +/- 32.9 pg/ml, respectively; p = 0.0012). In AD patients, the plasma p3-Alc alpha concentration significantly correlated with age (r = 0.23, p = 0.037) and serum creatinine levels (r = 0.23, p = 0.0012). Even after adjusting for confounding factors of age, gender, renal function, and ApoE-epsilon 4, high plasma p3-Alc alpha levels were correlated with significant AD risk, with an odds ratio 1.47 (95% confidence interval: 1.18-1.93, p = 0.0019) for every 10 pg/ml increase. Pooled analysis further confirmed these findings. Increased plasma p3-Alc alpha, evident in the early stages of cognitive impairment, suggests that Alc metabolites are useful plasma biomarkers of AD.