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

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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; Marklund, Niklas.

I: Brain Pathology, Vol. 28, Nr. 4, 07.2018, s. 451-462.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Abu Hamdeh, S, Waara, ER, Möller, C, Söderberg, L, Basun, H, Alafuzoff, I, Hillered, L, Lannfelt, L, Ingelsson, M & Marklund, N 2018, 'Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury', Brain Pathology, vol. 28, nr. 4, s. 451-462. https://doi.org/10.1111/bpa.12532

APA

Abu Hamdeh, S., Waara, E. R., Möller, C., Söderberg, L., Basun, H., Alafuzoff, I., ... Marklund, N. (2018). Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury. Brain Pathology, 28(4), 451-462. https://doi.org/10.1111/bpa.12532

CBE

Abu Hamdeh S, Waara ER, Möller C, Söderberg L, Basun H, Alafuzoff I, Hillered L, Lannfelt L, Ingelsson M, Marklund N. 2018. Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury. Brain Pathology. 28(4):451-462. https://doi.org/10.1111/bpa.12532

MLA

Vancouver

Abu Hamdeh S, Waara ER, Möller C, Söderberg L, Basun H, Alafuzoff I et al. Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury. Brain Pathology. 2018 jul;28(4):451-462. https://doi.org/10.1111/bpa.12532

Author

Abu Hamdeh, Sami ; Waara, Erik Rollman ; Möller, Christer ; Söderberg, Linda ; Basun, Hans ; Alafuzoff, Irina ; Hillered, Lars ; Lannfelt, Lars ; Ingelsson, Martin ; Marklund, Niklas. / Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury. I: Brain Pathology. 2018 ; Vol. 28, Nr. 4. s. 451-462.

RIS

TY - JOUR

T1 - Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury

AU - Abu Hamdeh, Sami

AU - Waara, Erik Rollman

AU - Möller, Christer

AU - Söderberg, Linda

AU - Basun, Hans

AU - Alafuzoff, Irina

AU - Hillered, Lars

AU - Lannfelt, Lars

AU - Ingelsson, Martin

AU - Marklund, Niklas

PY - 2018/7

Y1 - 2018/7

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid β oligomers

KW - Amyloid-β

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=85020546043&partnerID=8YFLogxK

U2 - 10.1111/bpa.12532

DO - 10.1111/bpa.12532

M3 - Article

VL - 28

SP - 451

EP - 462

JO - Brain Pathology

T2 - Brain Pathology

JF - Brain Pathology

SN - 1750-3639

IS - 4

ER -