Association of increased cortical soluble Aβ42 levels with diffuse plaques after severe brain injury in humans

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 (A beta) 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) A beta peptides are posited to disrupt synaptic function and are associated with cognitive decline in Alzheimer disease. Changes in soluble A beta levels and their relationship to A beta plaque formation following TBI are unknown. Objective: To quantify brain tissue levels of soluble A beta peptides and their precursor protein in relation to A beta plaque formation after TBI in humans. Design: Surgically resected temporal cortex tissue from patients with severe TBI was processed for biochemical assays of soluble A beta peptides with COOH-termini ending in amino acid 40 (A beta(40)) or 42 (A beta(42)) and A beta precursor protein to compare patients with cortical A beta 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 A beta(1-42) but not A beta(1-40); half of them were apolipoprotein E (APOE) epsilon 4 allele carriers. The lowest A beta levels were in 1 patient without plaques who was the only subject with an APOE epsilon 2 allele. beta-Amyloid precursor protein levels were comparable in the 2 TBI groups. Conclusions: Selective increases in soluble A beta(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.