βA4 amyloid protein deposition in brain after head trauma

Roberts, Gareth W.; Gentleman, Stephen M.; Lynch, Aoibhinn; Graham, David I.

doi:10.1016/0140-6736(91)92724-g

Cited by 456 publications

(242 citation statements)

References 8 publications

Supporting

Mentioning

232

Contrasting

Unclassified

Order By: Relevance

“…Clinical and experimental TBI is also associated with accelerated A␤ deposition (Roberts et al, 1991), with an even greater effect observed in APOE4ϩ individuals on both parenchymal and vascular A␤ deposits (Nicoll et al, 1995(Nicoll et al, , 1996Macfarlane et al, 1999;Leclercq et al, 2002). A␤ deposition is also accelerated after seizure-induced neurodegeneration, even in young APOE4ϩ subjects (Gouras et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…These risk factors appear to act synergistically, in that individuals who are APOE4ϩ are even more likely to develop dementia if they sustain TBI at some time in their life. For example, APOE4ϩ individuals were 10 times more likely to develop AD after TBI than those who were APOE4Ϫ, whereas APOE4 in the absence of injury was associated with only twice the risk (Mayeux et al, 1995;Tang et al, 1996).Although the mechanisms underlying these effects are unclear, some evidence suggests that both APOE4 and TBI may influence the risk of AD via interactions with the amyloid-␤ (A␤) peptide.For example, A␤ deposition can be found in ϳ30% of people who die shortly after TBI (Roberts et al, 1991(Roberts et al, , 1994; a significant percentage of these patients are APOE4ϩ (Nicoll et al, 1995(Nicoll et al, , 1996. In addition, analysis of CSF from TBI patients revealed elevated levels of A␤ 1-42 for up to a week after TBI, in comparison with both controls and AD patients (Raby et al, 1998;Emmerling et al, 2000).…”

mentioning

confidence: 99%

“…For example, A␤ deposition can be found in ϳ30% of people who die shortly after TBI (Roberts et al, 1991(Roberts et al, , 1994; a significant percentage of these patients are APOE4ϩ (Nicoll et al, 1995(Nicoll et al, , 1996. In addition, analysis of CSF from TBI patients revealed elevated levels of A␤ 1-42 for up to a week after TBI, in comparison with both controls and AD patients (Raby et al, 1998;Emmerling et al, 2000).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Apolipoprotein E4 Influences Amyloid Deposition But Not Cell Loss after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease

et al. 2002

View full text Add to dashboard Cite

The ⑀4 allele of apolipoprotein E (APOE) and traumatic brain injury (TBI) are both risk factors for the development of Alzheimer's disease (AD). These factors may act synergistically, in that APOE4ϩ individuals are more likely to develop dementia after TBI. Because the mechanism underlying these effects is unclear, we questioned whether APOE4 and TBI interact either through effects on amyloid-␤ (A␤) or by enhancing cell death/tissue injury. We assessed the effects of TBI in PDAPP mice (transgenic mice that develop AD-like pathology) expressing human APOE3 (PDAPP: E3), human APOE4 (PDAPP:E4), or no APOE (PDAPP:EϪ/Ϫ). Mice were subjected to a unilateral cortical impact injury at 9-10 months of age and allowed to survive for 3 months. A␤ load, hippocampal/cortical volumes, and hippocampal CA3 cell loss were quantified using stereological methods. All of the groups contained mice with A␤-immunoreactive deposits (56% PDAPP: E4, 20% PDAPP:E3, 75% PDAPP:EϪ/Ϫ), but thioflavine-Spositive A␤ (amyloid) was present only in the molecular layer of the dentate gyrus in the PDAPP:E4 mice (44%). In contrast, our previous studies showed that in the absence of TBI, PDAPP:E3 and PDAPP:E4 mice have little to no A␤ deposition at this age. After TBI, all of the A␤ deposits present in PDAPP:E3 and PDAPP: EϪ/Ϫ mice were diffuse plaques. In contrast to the effect of APOE4 on amyloid, PDAPP:E3, PDAPP:E4, and PDAPP:EϪ/Ϫ mice did not differ in the amount of brain tissue or cell loss. These data support the hypothesis that APOE4 influences the neurodegenerative cascade after TBI via an effect on A␤.Key words: Alzheimer's disease; amyloid; APP; traumatic brain injury; apoE; hippocampus The ⑀4 allele of apolipoprotein E (APOE) and traumatic brain injury (TBI) are both risk factors for the development of Alzheimer's disease (AD). It was first found that APOE4 was a risk factor for AD in 1993 (Strittmatter et al., 1993), and numerous studies have confirmed this association. Several studies have found that individuals who sustained moderate to severe head injury are more likely to develop dementia and AD (Mayeux et al., 1993(Mayeux et al., , 1995Plassman et al., 2000). These risk factors appear to act synergistically, in that individuals who are APOE4ϩ are even more likely to develop dementia if they sustain TBI at some time in their life. For example, APOE4ϩ individuals were 10 times more likely to develop AD after TBI than those who were APOE4Ϫ, whereas APOE4 in the absence of injury was associated with only twice the risk (Mayeux et al., 1995;Tang et al., 1996).Although the mechanisms underlying these effects are unclear, some evidence suggests that both APOE4 and TBI may influence the risk of AD via interactions with the amyloid-␤ (A␤) peptide.For example, A␤ deposition can be found in ϳ30% of people who die shortly after TBI (Roberts et al., 1991(Roberts et al., , 1994; a significant percentage of these patients are APOE4ϩ (Nicoll et al., 1995(Nicoll et al., , 1996. In addition, analysis of CSF from TBI patients revealed elevated levels of ...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Apolipoprotein E4 Influences Amyloid Deposition But Not Cell Loss after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Several observations support this hypothesis. Among them: (i) augmented expression of the APP gene transcripts in Down's syndrome and in specific areas of the brain of AD patients (2-5); (ii) in vitro degeneration of postmitotic neurons overexpressing fulllength APP (6); (iii) marked increase of the APP gene expression after head trauma, a well-recognized enviromental risk factor for AD (7).…”

mentioning

confidence: 99%

Identification and Characterization of a κB/Rel Binding Site in the Regulatory Region of the Amyloid Precursor Protein Gene

Grilli

Ribola

Alberici

et al. 1995

Journal of Biological Chemistry

View full text Add to dashboard Cite

Several observations support the hypothesis that pathogenetic mechanisms of ␤ amyloid formation in Alzheimer's disease may involve alterations in amyloid precursor protein (APP) gene expression. In this regard, molecular dissection of the APP gene transcriptional regulation is of primary importance. We report evidence that members of the family of transcription factors NFB/Rel can specifically recognize two identical sequences located in the 5-regulatory region of APP. These sequences, which we refer to as APPB sites, interact preferentially with p50-containing members of the family. In particular, p50 homodimers and p50/p65 and p50/c-Rel heterodimers act as transcriptional activators at the APPB site. Finally, the nuclear complex specifically binding to the APPB sites proves to be an integral part of neurons and lymphocytes.

show abstract

“…The interest in the role of Ab after TBI has grown from epidemiological studies that have demonstrated an association between a history of TBI and the development of AD later in life (Graves et al, 1990;Mortimer et al, 1985Mortimer et al, , 1991Salib and Hillier, 1997;Szczygielski et al, 2005;Van Den Heuvel et al, 2007). Additionally, post-mortem studies have demonstrated AD-like deposits of Ab in as many as 30% of TBI victims (Roberts et al, 1991(Roberts et al, , 1994. These observations have led to interest in Ab as a therapeutic target after TBI.…”

Section: Introductionmentioning

confidence: 99%

Detrimental Effect of Genetic Inhibition of B-Site App-Cleaving Enzyme 1 on Functional Outcome after Controlled Cortical Impact in Young Adult Mice

Mannix

Zhang

Park

et al. 2011

Journal of Neurotrauma

View full text Add to dashboard Cite

Abstractb-Amyloid (Ab) peptides, most notably associated with Alzheimer's disease, have been implicated in the pathogenesis of secondary injury after traumatic brain injury (TBI). A prior study has demonstrated that blocking the b-site amyloid precursor protein (APP)-cleaving enzyme 1 (Bace1) required for production of Ab from APP improved functional and histologic outcomes after controlled cortical impact (CCI) in aged mice. However, the majority of patients with severe TBI are young adults under the age of 40. Prior experimental models have suggested age-dependent differences in Ab clearance, and a recent study in our lab suggests that young animals remediate acute elevations in Ab after CCI better than older animals. We therefore tested the hypothesis that Bace1 deletion in young adult mice would not be protective after CCI. Male Bace1 knockout (Bace1 -/-) and wild-type Bace1 +/+ (C57BL/6) mice (2-3 months old) were subjected to CCI (n = 18-23/group) or sham injury (n = 10-12/group). Functional outcomes were assessed with wire grip (motor) and the Morris water maze (MWM; spatial memory). Soluble Ab levels were assessed at 48 h after CCI. Histopathological outcomes were assessed by lesion and hippocampal volume. Clustered ordinal logistic regression showed overall significant impairment in motor performance in injured Bace1-/-versus Bace1 +/+ animals ( p = 0.003). No significant differences in MWM performance were found on repeated-measures ANOVA ( p = 0.11) between groups. Probe scores were significantly worse in injured Bace1-/-versus Bace1 +/+ mice ( p = 0.0009). Soluble Ab 40 was significantly lower in ipsilateral hemispheres of Bace1 -/-than in Bace1 +/+ animals after CCI (0.9 [IQR 0.88-0.94] pmol/g protein versus 3.8 [IQR 2.4-6.0] pmol/g protein; p = 0.005). Lesion and hippocampal volumes did not differ between injured groups. The data suggest that therapies targeting Bace1 may need to be tailored according to age and injury severity, as their use may exacerbate functional deficits after TBI in younger or less severely injured patients.

show abstract

βA4 amyloid protein deposition in brain after head trauma

Cited by 456 publications

References 8 publications

Apolipoprotein E4 Influences Amyloid Deposition But Not Cell Loss after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease

Apolipoprotein E4 Influences Amyloid Deposition But Not Cell Loss after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease

Identification and Characterization of a κB/Rel Binding Site in the Regulatory Region of the Amyloid Precursor Protein Gene

Detrimental Effect of Genetic Inhibition of B-Site App-Cleaving Enzyme 1 on Functional Outcome after Controlled Cortical Impact in Young Adult Mice

Contact Info

Product

Resources

About