ABSTRACT
Objective: Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analysed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI.
Methods: Highly selective ELISAs were used to analyse N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n=12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/haemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n=5), to post-mortem tissue of neurologically intact subjects (n=4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n=4).
Results: The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to neurologically intact and iNPH controls (P<0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n=4) had increased levels of Aβ oligomers/protofibrils (P<0.05) and of both N-terminally intact and truncated Aβ42 (P<0.05) compared to APOE ε3/4-negative TBI patients (n=8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers.
Interpretation: Soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI. This article is protected by copyright. All rights reserved.
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