Traumatic brain injury (TBI) is an environmental risk factor for developing Alzheimer disease. This may be due, in part, to changes associated with β-amyloid (Aβ) 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) Aβ peptides are posited to disrupt synaptic function and are associated with cognitive decline in Alzheimer disease. Changes in soluble Aβ levels and their relationship to Aβ plaque formation following TBI are unknown.
To quantify brain tissue levels of soluble Aβ peptides and their precursor protein in relation to Aβ plaque formation after TBI in humans.
Surgically resected temporal cortex tissue from patients with severe TBI was processed for biochemical assays of soluble Aβ peptides with COOH-termini ending in amino acid 40 (Aβ40) or 42 (Aβ42) and Aβ precursor protein to compare patients with cortical Aβ plaques and those without.
Nineteen subjects admitted to the University of Pittsburgh Medical Center for treatment of severe closed head injury.
Patients with severe TBI and cortical plaques had higher levels of soluble Aβ1-42 but not Aβ1-40; half of them were apolipoprotein E (APOE) ε4 allele carriers. The lowest Aβ levels were in 1 patient without plaques who was the only subject with an APOE ε2 allele. β-Amyloid precursor protein levels were comparable in the 2 TBI groups.
Selective increases in soluble Aβ1-42 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.