Beta-amyloid deposition in chronic traumatic encephalopathy

Stein, Thor D.; Montenigro, Philip H.; Alvarez, Victor E.; Xia, Weiming; Crary, John F.; Tripodis, Yorghos; Daneshvar, Daniel H.; Mez, Jesse; Solomon, Todd M.; Meng, Guowang; Kubilus, Caroline A.; Cormier, Kerry; Meng, Steven; Babcock, Katharine J.; Kiernan, Patrick T.; Murphy, Lauren; Nowinski, Christopher J.; Martin, Brett; Dixon, Diane; Stern, Robert A.; Cantu, Robert C.; Kowall, Neil W.; McKee, Ann C.

doi:10.1007/s00401-015-1435-y

Cited by 246 publications

(249 citation statements)

References 54 publications

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“…CTE is primarily known as a tauopathy; however, because 52% of 114 neuropathologically confirmed CTE brains also demonstrate concomitant Ab plaque deposition, 11 we wanted to introduce a mouse model that has the ability to produce both amyloid and tau pathology. The 3xTg-AD mouse overexpresses mutant human APP and tau, leading to amyloid plaques and tau tangles in the brain.…”

Section: Rmtbi Does Not Induce Amyloid or Tau Pathology In 3xtg-ad Micementioning

confidence: 99%

“…9,10 This disease is associated primarily with the buildup of neurofibrillary tangles of hyperphosphorylated tau throughout the brain; however, 52% of cases also present with diffuse amyloid-b (Ab) deposits. 11 There has been difficulty reproducing tau pathology in rodents after rmTBI, and to date the only study that has seen a chronic (21 days after TBI) increase in hyperphosphorylated tau after rmTBI has required the use of aged tau transgenic mice to observe an effect. 12 In this study, we examine changes to the neuronal structure and brain pathology after a single mTBI or rmTBI.…”

mentioning

confidence: 99%

“…We establish the effect of a 60-and 365-day period of convalescence on pathology, and the effect of increasing the interinjury interval from 1 to 7 days. Because the cumulative effects of rmTBI may cause the development of CTE in humans, and a recent study showed that 52% of CTE brains have both amyloid and tau pathology, 11 we also explore the effects of rmTBI on concurrent amyloid and tau pathology in a mouse model of Alzheimer disease (3ÂTg-AD) that develops both types of pathology.…”

mentioning

confidence: 99%

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Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Winston

Noël

Neustadtl

et al. 2016

The American Journal of Pathology

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Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase b-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact. (Am J Pathol 2016, 186: 552e567; http://dx.doi.org/ 10.1016/j.ajpath.2015 Athletes participating in contact sports are at high risk of exposure to large numbers of concussive and subconcussive mild traumatic brain injuries (mTBIs). Recent studies using head impact telemetry systems have begun to reveal how many head impacts an individual football player can receive in the process of playing his or her sport. In a study of high school football players, the number of helmet impacts >20 g recorded in a single season ranged from a low of 226 (average, 4.7 per session) to a high of 1855 (average, 38.6 per session). 1 Most of these impacts do not result in the clinical diagnosis of a concussion; however, it is not known if the cumulative effects of these impacts can result in increased damage to the brain. mTBI has been extensively modeled in mice and rats. 2 Most of these rodent models use fewer than five mTBIs, and report adverse events, including intracerebral bleeding, skull fractures, severe axonal injury, neuronal cell death, and increased mortality.

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Section: Rmtbi Does Not Induce Amyloid or Tau Pathology In 3xtg-ad Micementioning

confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Winston

Noël

Neustadtl

et al. 2016

The American Journal of Pathology

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“…They also controls genes regulating cell changes, including cell proliferation, survival and oxidative defense (23). It has been indicated that the decrease of FoxOs in hematopoietic stem cells may cause a decrease in antioxidase including reactive oxygen species, manganese superoxide dismutase and scavenger enzymes, resulting in dysfunction of mitochondria and cell apoptosis (24).…”

Section: Discussionmentioning

confidence: 99%

Anti‑aging effect of fullerenol on skin aging through derived stem cells in a mouse model

Sui

et al. 2017

Exp Ther Med

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Abstract.Fullerenol is similar to graphite in terms of structure. In the present study, the anti-aging effect of fullerenol on skin through derived stem cells in a mouse model was assessed and the potential mechanism of fullerenol was investigated. The anti-aging effect of fullerenol effectively inhibited the retention rate of transplanted adipose-derived stem cells and increased the thickness of the dermal portion of skin and collagen ratio in mice. The effect of fullerenol on the proliferation of stem cells was observed. Treatment with fullerenol effectively promoted the mRNA expression of Runt-related transcription factor 2, alkaline phosphatase and osteocalcin in a mouse model of skin aging induced by D-galactose. However, fullerenol treatment effectively suppressed the protein expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased forkhead box protein O1 (FoxO1) protein expression in the mice model of skin aging induced by D-galactose. These results demonstrate that the anti-aging effect of fullerenol on skin through derived stem cells may be mediated in mice via the PPAR-γ/FoxO1 signaling pathway.

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“…[16][17][18] Patients with AD can have memory loss, mood swings, and agitation, just as patients with CTE can have those same symptoms. CTE is defined pathologically by the abnormal accumulation of the tau protein in a pattern that is different from other tauopathies, such as AD and FTD.…”

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confidence: 99%

Memory loss

et al. 2016

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Purpose of review: Memory loss can be due to a wide variety of causes. We provide new information about the biology of common genetic and acquired causes of memory loss in older adults. Recent findings:New data are available about the genetics of Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia. Amyloid PET, FDG-PET, and MRI have improved our understanding of how mild cognitive impairment evolves to AD. Several studies have shown links between concussion and chronic traumatic encephalopathy. Healthy eating and regular exercise have been demonstrated to slow cognitive decline in older adults. Randomized trials continue to show benefits for cholinesterase inhibitors and memantine in patients with AD and DLB. Summary: New causes of memory loss are still being identified. More sophisticated diagnostic tools have improved our ability to make earlier diagnoses in older adults with memory loss. Neurol Clin Pract 2016;6:523-529 R ecent large neuropathologic studies have shown that Alzheimer disease (AD) is still the most common of the chronic neurodegenerative memory disorders, but it is often associated with several comorbid histologic findings, such as cortical Lewy bodies, hippocampal sclerosis, and microinfarcts. Amyloid hypothesis and the genetics of AD While it is well-accepted that memory loss and other cognitive impairments in AD are the result of dysfunction in neuronal networks and synapses, the exact molecular and pathologic steps generating the clinical symptoms of AD remain an issue of some debate. Some have argued that b-amyloid (Ab) is a necessary but insufficient factor to explain the etiology of AD, arguing that Ab aggregations in the brain and decreased Ab levels in spinal fluid are detectable 15-20 years before the clinical symptoms of AD.2 Contradicting this view are recent findings from the Alzheimer's Disease Neuroimaging Initiative (ADNI), which demonstrated that decreases in CSF Ab levels are often not apparent until after there is a noticeable decline in cognitive function, a decline in metabolic activity on FDG-PET, and

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Beta-amyloid deposition in chronic traumatic encephalopathy

Cited by 246 publications

References 54 publications

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Anti‑aging effect of fullerenol on skin aging through derived stem cells in a mouse model

Memory loss

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