title: Potential utility of soluble p3-alcadein α plasma levels as a biomarker for sporadic Alzheimer's disease.
abstract: Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins (α, β, γ) that share identical localization and function to the amyloid-β protein precursor (AβPP) in the brain. Alcs are proteolyzed in neurons through successive cleavages via secretases, resulting in non-aggregative p3-Alc, where p3 corresponds to the AβPP-fragment. We found p3-Alcα detected in human plasma reflected the pathological process of amyloid-β accumulation in Alzheimer's disease (AD) patients and therefore investigated the utility of p3-Alcα as a plasma biomarker in AD. We measured p3-Alcα 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-Alcα 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-Alcα 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-ε4, high plasma p3-Alcα 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-Alcα, evident in the early stages of cognitive impairment, suggests that Alc metabolites are useful plasma biomarkers of AD.
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kamogawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Rie
authors.initials: R
authors.lastname: Takita
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Konno
authors.forename: Saori
authors.initials: S
authors.lastname: Hata
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C503225:CLSTN1 protein, human; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins