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Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury

Abu Hamdeh, Sami; Waara, Erik Rollman; Möller, Christer; Söderberg, Linda; Basun, Hans; Alafuzoff, Irina; Hillered, Lars; Lannfelt, Lars; Ingelsson, Martin and Marklund, Niklas LU (2017) In Brain Pathology
Abstract

Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze 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/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n=5), to post-mortem tissue of... (More)

Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze 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/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n=5), to post-mortem tissue of neurologically intact (NI) subjects (n=4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n=4). 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 NI 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. We conclude that 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.

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author
publishing date
type
Contribution to journal
publication status
epub
keywords
Alzheimer's disease, Amyloid β oligomers, Amyloid-β, Traumatic brain injury
in
Brain Pathology
publisher
Wiley-Blackwell
external identifiers
  • scopus:85020546043
ISSN
1015-6305
DOI
10.1111/bpa.12532
language
English
LU publication?
no
id
cc06da4d-d6ea-41a4-b8e5-5e06c65c8a99
date added to LUP
2018-03-03 16:51:04
date last changed
2018-08-05 04:48:07
@article{cc06da4d-d6ea-41a4-b8e5-5e06c65c8a99,
  abstract     = {<p>Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze 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/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n=5), to post-mortem tissue of neurologically intact (NI) subjects (n=4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n=4). 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 NI and iNPH controls (P&lt;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&lt;0.05) and of both N-terminally intact and truncated Aβ42 (P&lt;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. We conclude that 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.</p>},
  author       = {Abu Hamdeh, Sami and Waara, Erik Rollman and Möller, Christer and Söderberg, Linda and Basun, Hans and Alafuzoff, Irina and Hillered, Lars and Lannfelt, Lars and Ingelsson, Martin and Marklund, Niklas},
  issn         = {1015-6305},
  keyword      = {Alzheimer's disease,Amyloid β oligomers,Amyloid-β,Traumatic brain injury},
  language     = {eng},
  publisher    = {Wiley-Blackwell},
  series       = {Brain Pathology},
  title        = {Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury},
  url          = {http://dx.doi.org/10.1111/bpa.12532},
  year         = {2017},
}