title: Association of increased cortical soluble abeta42 levels with diffuse plaques after severe brain injury in humans.
abstract: BACKGROUND
  Traumatic brain injury (TBI) is an environmental risk factor for developing Alzheimer disease. This may be due, in part, to changes associated with beta-amyloid (Abeta) plaque formation, which can occur within hours after injury, regardless of the patient's age. In addition to being precursors of toxic fibrils that deposit into plaques, soluble (nonfibrillar) Abeta peptides are posited to disrupt synaptic function and are associated with cognitive decline in Alzheimer disease. Changes in soluble Abeta levels and their relationship to Abeta plaque formation following TBI are unknown.
  
  
  OBJECTIVE
  To quantify brain tissue levels of soluble Abeta peptides and their precursor protein in relation to Abeta plaque formation after TBI in humans.
  
  
  METHODS
  Surgically resected temporal cortex tissue from patients with severe TBI was processed for biochemical assays of soluble Abeta peptides with COOH-termini ending in amino acid 40 (Abeta(40)) or 42 (Abeta(42)) and Abeta precursor protein to compare patients with cortical Abeta plaques and those without. Patients Nineteen subjects admitted to the University of Pittsburgh Medical Center for treatment of severe closed head injury.
  
  
  RESULTS
  Patients with severe TBI and cortical plaques had higher levels of soluble Abeta(1-42) but not Abeta(1-40); half of them were apolipoprotein E (APOE) epsilon4 allele carriers. The lowest Abeta levels were in 1 patient without plaques who was the only subject with an APOE epsilon2 allele. beta-Amyloid precursor protein levels were comparable in the 2 TBI groups.
  
  
  CONCLUSIONS
  Selective increases in soluble Abeta(1-42) after TBI may predispose individuals with a brain injury to Alzheimer disease pathology. This may be influenced by the APOE genotype, and it may confer increased risk for developing Alzheimer disease later in life.
authors.affiliation: Department of Neurology, University of Pittsburgh, 3471 Fifth Ave, Suite 811, Pittsburgh, PA 15213, USA. dekoskyst@upmc.edu
authors.forename: Steven T
authors.initials: ST
authors.lastname: DeKosky
authors.forename: Eric E
authors.initials: EE
authors.lastname: Abrahamson
authors.forename: John R
authors.initials: JR
authors.lastname: Ciallella
authors.forename: William R
authors.initials: WR
authors.lastname: Paljug
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D015153:Blotting, Western; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)