title: Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairment.
abstract: OBJECTIVE
  To evaluate the relations between PET Pittsburgh compound B (PiB-PET) binding (amyloid imaging) and plasma Aβ in patients with mild cognitive impairment (MCI) and similarly aged controls.
  
  
  METHODS
  In 20 patients with MCI and 19 cognitively intact controls (case-control study), PiB binding potential (BP(nd)) was assessed in 4 regions, and total brain excluding cerebellum, referenced to cerebellar binding. The mean of plasma Aβ levels measured in duplicate was analyzed.
  
  
  RESULTS
  Plasma Aβ42/Aβ40 ratio was decreased in MCI compared to controls (mean 0.15 SD 0.04 vs mean 0.19 SD 0.07, p = 0.03) but Aβ40 (p = 0.3) and Aβ42 (p = 0.06) levels did not differ between the 2 groups. PiB BP(nd) was increased in MCI compared to controls in the cingulate (p = 0.02), parietal (p = 0.02), and total brain (p = 0.03), but not in prefrontal cortex (p = 0.08) or parahippocampal gyrus (p = 0.07). Linear regression analyses adjusting for age, sex, and cognitive test scores showed that low Aβ42/Aβ40 ratio was associated with high cingulate, parietal, and total brain PiB binding (0.01< p ≤ 0.05). These associations between PiB binding and the Aβ42/Aβ40 ratio were strongest in PiB-positive subjects and within the MCI group.
  
  
  CONCLUSIONS
  Though cross-sectional, the findings support the "sink" hypothesis that increased brain Aβ is accompanied by lower peripheral levels of Aβ, particularly the Aβ42/Aβ40 ratio in patients with MCI. The association between PiB binding and the plasma Aβ42/Aβ40 ratio suggests possible use of plasma Aβ combined with PiB binding as a risk biomarker with potential clinical application.
authors.affiliation: Divisions of Geriatric Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA. dpd3@columbia.edu
authors.forename: D P
authors.initials: DP
authors.lastname: Devanand
authors.forename: N
authors.initials: N
authors.lastname: Schupf
authors.forename: Y
authors.initials: Y
authors.lastname: Stern
authors.forename: R
authors.initials: R
authors.lastname: Parsey
authors.forename: G H
authors.initials: GH
authors.lastname: Pelton
authors.forename: P
authors.initials: P
authors.lastname: Mehta
authors.forename: R
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000097:blood*; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000493:pharmacokinetics*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000097:blood* / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)