Researchers discover how TBI can lead to Alzheimer’s disease and chronic traumatic encephalopathy
New research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) provides the first direct evidence linking traumatic brain injury to Alzheimer’s disease and chronic traumatic encephalopathy (CTE) — and offers the potential for early intervention to prevent the development of these debilitating neurodegenerative diseases.
TBI can result from repetitive contact sport injuries or from exposure to military blasts, and is one of the most significant risk factors for both Alzheimer’s disease and CTE.
In a study published today in the online edition of the journal Nature, the researchers found that a misshapen isoform of the tau protein can develop as soon as 12 hours after TBI, setting in motion a destructive course of events that can lead to widespread neurodegeneration. Importantly, the researchers have developed a potent antibody that can selectively detect and destroy this highly toxic protein.
“TBI is a leading cause of death and disability in children and young adults and also affects approximately 20 percent of the more than two million troops who have deployed to Iraq and Afghanistan,” said co-senior author Kun Ping Lu, MD, PhD, Chief of the Division of Translational Therapeutics in the Department of Medicine at BIDMC and Professor of Medicine at Harvard Medical School (HMS). “Our study shows that an early neurodegenerative process induced by the toxic tau protein can begin just hours after a traumatic brain injury. In both cell models of stress and in mouse models simulating sport- and military-related TBI, the production of this pathogenic protein, called cis P-tau, disrupts normal neurological functioning, spreads to other neurons and leads to widespread neuronal death. We have developed a potent monoclonal antibody that can prevent the onset of widespread neurodegeneration by identifying and neutralizing this toxic protein and restoring neurons’ structural and functional abilities.”
Alzheimer’s disease is the most common form of dementia in older individuals and currently affects more than 5 million Americans and 30 million people worldwide. Chronic traumatic encephalopathy is a degenerative brain disease associated with a number of neurological symptoms including risk-taking, aggression and depression. CTE can also lead to progressive dementia.
Previous research has shown that abnormal phosphorylation of the tau protein underlies Alzheimer’s and other neurodegenerative diseases. In recent years, the Lu laboratory discovered that tau exists in two isoforms, or shapes –¬ ¬¬one functioning and one disease-causing.
“Healthy tau protein is found in the brain and serves to assemble and support microtubules, the ‘scaffolding systems’ that give neurons their unique shape and are integral to memory and normal brain functioning,” explained Lu. But in Alzheimer’s, CTE and other neurodegenerative diseases, collectively called tauopathies, tau becomes tangled and unable to function properly.
“Recent studies of CTE in the brains of boxers, American football players and blast-exposed veterans have identified extensive neurofibrillary tau tangles,” he said. “But, because these tangles were not detected until months or, more likely, years after TBI, it has not been known whether tauopathy is a cause or a consequence of TBI-related neurodegenerative disease. We have now shown that it is a cause of these diseases.”
The Latest on: Neurodegeneration antibody
via Google News
The Latest on: Neurodegeneration antibody
- We need to radically rethink our approach to Alzheimer’s researchon January 29, 2020 at 10:07 pm
A unifying feature of neurodegeneration is the accumulation of sticky protein deposits within ... Whether protein deposits are mopped up by antibodies, or inhibited from forming in the first place, ...
- A Comparison Between the Tau Hypothesis and the Amyloid Hypothesison January 27, 2020 at 12:28 am
10 Atomic structure of the Alzheimer’s disease Amyloid-β protein caged by four shark antibodies to stop uncontrolled amyloid plaque formation. Four interacting Amyloid-β fragments are outlined by grey ...
- Alzheimer’s Disease and the Role of Tau Phosphorylationon January 26, 2020 at 11:42 pm
AT8 was the first of these antibodies to enter mainstream utilization ... Yet, multiple residues flanking the microtubule binding domains of human tau are particularly implicated in neurodegeneration.
- Focused ultrasound delivery of a selective TrkA agonist rescues cholinergic function in a mouse model of Alzheimer’s diseaseon January 22, 2020 at 12:51 pm
Neuroprotective agents targeting TrkA, combined with MRIgFUS BBB modulation, represent a promising strategy to counter neurodegeneration in AD ... with 5% bovine serum albumin in tris-buffered ...
- Golgi organization is regulated by proteasomal degradationon January 21, 2020 at 4:05 am
Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer ... Cells were blocked in 2% BSA and primary antibodies were introduced for 1 h and secondary ...
- Novel dementia vaccine on track for human trials within two yearson December 31, 2019 at 4:00 pm
A newly published study has described the successful results in mice of a novel vaccine designed to prevent neurodegeneration ... a vaccine designed to generate antibodies that both prevent ...
- AbbVie And Voyager Therapeutics Collaborate To Develop Vectorized Antibodieson February 22, 2019 at 5:14 am
(RTTNews) - AbbVie (ABBV) and Voyager Therapeutics Inc. (VYGR) announced collaboration and option agreement to develop and commercialize vectorized antibodies directed at pathological species of ...
- 'Promising' Preliminary Results for Antibody in Parkinson'son June 26, 2018 at 5:00 pm
The antibody is directed against the protein ... Parkinson's primarily target symptoms but do not slow or halt the underlying neurodegeneration. This new strategy is a different approach targeting ...
- This Week in Scienceon July 28, 2017 at 4:49 am
Science, this issue p. 586 Understanding the specificity and sensitivity of antibodies is important for interpreting experimental data generated with these reagents. Frohner et al. found that ...
- Neurodegeneration: Antibody therapy reduces amyloid plaques in Alzheimer’s diseaseon August 31, 2016 at 5:00 pm
An antibody therapy that reduces amyloid beta deposits in ... Amyloid beta-related toxicity is thought to be a primary cause of the synaptic dysfunction and neurodegeneration that underlies the ...
via Bing News