title: Elevation of the Plasma Aβ40/Aβ42 Ratio as a Diagnostic Marker of Sporadic Early-Onset Alzheimer's Disease.
abstract: BACKGROUND
  Although plasma amyloid-β (Aβ) levels have been evaluated as a possible diagnostic marker of Alzheimer's disease (AD), the findings are inconsistent.
  
  
  OBJECTIVE
  The present study aimed to validate plasma levels of Aβ40, Aβ42, and the Aβ40/Aβ42 ratio as biomarkers of AD in subjects with early-onset AD (EOAD) without familial AD genetic mutations.
  
  
  METHODS
  Patients with sporadic EOAD (sEOAD) were prospectively recruited by nine neurology clinics. Plasma levels of Aβ40 and Aβ42 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) in 100 sEOAD (50-69 year-old) and 46 age-matched normal control subjects (50-72 year-old). Cerebrospinal fluid (CSF) was obtained from 32 sEOAD subjects and 25 controls. The integrity of the blood-brain barrier was assessed using the CSF/plasma albumin ratio.
  
  
  RESULTS
  The plasma levels of Aβ42 were significantly lower, while the Aβ40/Aβ42 ratio was significantly higher in sEOAD patients than in controls. The levels of Aβ40, Aβ42, and the Aβ40/Aβ42 ratio did not differ in relation to the APOEɛ4 allele. The CSF/plasma albumin ratio was comparable between the two groups, and the plasma parameters of Aβ proteins were not significantly associated. A multivariate analysis revealed that an increased Aβ40/Aβ42 ratio is valuable for the discrimination of sEOAD from controls (β=0.344, p=0.000). The area under the ROC curve for the Aβ40/Aβ42 ratio was 0.76, and a cut-off ratio of 5.87 was suggested to have 70% sensitivity and 68% specificity.
  
  
  CONCLUSIONS
  The plasma Aβ40/Aβ42 ratio had moderate validity for the discrimination of sEOAD patients from age-matched controls.
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Dong-A University College of Medicine, Dong-A University Hospital, Busan, Korea.
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Park
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Tae Eun
authors.initials: TE
authors.lastname: Kim
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Im
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Ho Sik
authors.initials: HS
authors.lastname: Shin
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Saeromi
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byoung Seok
authors.initials: BS
authors.lastname: Ye
authors.affiliation: Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, Goyang, Korea.
authors.forename: Jong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Pusan National University Hospital, Busan, Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Gachon University, College of Medicine, Incheon, Korea.
authors.forename: Kee Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Neurology, Myongii Hospital, Seonam University College of Medicine, Goyang, Korea.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Han
authors.affiliation: Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, Korea.
authors.forename: Jee Hyang
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Neurology, Inha University School of Medicine, Incheon, Korea.
authors.forename: Seong Hye
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Park
mesh_terms: D017668:Age of Onset; D000368:Aged; D000418:Albumins / Q000134:cerebrospinal fluid; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000235:genetics; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000378:metabolism; D002199:Capillary Permeability; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D000418:Albumins; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; D012709:Serum Albumin; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; amyloid-β protein; biomarker; blood-brain barrier; plasma