title: Distinct pools of beta-amyloid in Alzheimer disease-affected brain: a clinicopathologic study.
abstract: OBJECTIVE
  To determine whether beta-amyloid (Abeta) peptides segregated into distinct biochemical compartments would differentially correlate with clinical severity of Alzheimer disease (AD).
  
  
  METHODS
  Clinicopathologic correlation study.
  
  
  METHODS
  Twenty-seven patients from a longitudinal study of AD and 13 age- and sex-matched controls without a known history of cognitive impairment or dementia were included in this study.
  
  
  METHODS
  Temporal and cingulate neocortex were processed using a 4-step extraction, yielding biochemical fractions that are hypothesized to be enriched with proteins from distinct anatomical compartments: TRIS (extracellular soluble), Triton (intracellular soluble), sodium dodecyl sulfate (SDS) (membrane associated), and formic acid (extracellular insoluble). Levels of Abeta(40) and Abeta(42) were quantified in each biochemical compartment by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The Abeta(42) level in all biochemical compartments was significantly elevated in patients with AD vs controls (P < .01). The Abeta(40) levels in the TRIS and formic acid fractions were elevated in patients with AD (temporal, P < .01; cingulate, P = .03); however, Triton and SDS Abeta(40) levels were similar in patients with AD and in controls. Functional impairment proximal to death correlated with Triton Abeta(42) (r = 0.48, P = .02) and SDS Abeta(42) (r = 0.41, P = .04) in the temporal cortex. Faster cognitive decline was associated with elevated temporal SDS Abeta(42) levels (P < .001), whereas slower decline was associated with elevated cingulate formic acid Abeta(42) and SDS Abeta(42) levels (P = .02 and P = .01, respectively).
  
  
  CONCLUSIONS
  Intracellular and membrane-associated Abeta, especially Abeta(42) in the temporal neocortex, may be more closely related to AD symptoms than other measured Abeta species.
authors.affiliation: Departments of Neurology, Columbia University Medical Center, 630 W 168th St, P&S Box 16, New York, NY 10032, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Steinerman
authors.forename: Michael
authors.initials: M
authors.lastname: Irizarry
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Scarmeas
authors.forename: Susan
authors.initials: S
authors.lastname: Raju
authors.forename: Jason
authors.initials: J
authors.lastname: Brandt
authors.forename: Marilyn
authors.initials: M
authors.lastname: Albert
authors.forename: Deborah
authors.initials: D
authors.lastname: Blacker
authors.forename: Bradley
authors.initials: B
authors.lastname: Hyman
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D010054:Brief Psychiatric Rating Scale; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides