Traumatic Brain Injury (TBI) increases the risk for certain neurodegenerative diseases, such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE).
Research shows when a person experiences repetitive mild Traumatic Brain Injury (TBI), a condition called Amyloid-beta and Tau Pathology might develop. What does it mean? It means that two proteins, namely Abeta and Tau, misfold and turn into Misfolded Proteins, aka Prion Proteins.
In simple terms, we refer to them as Proteins Gone Rogue. When this happens, the two rogue proteins: Abeta and Tau, cause damage to the brain. Let’s take a sneak peek at the molecular footprint of Traumatic Brain Injury.
What’s neurodegenerative diseases:
In general terms, neurodegenerative diseases are characterized by distinctive neuropathological alterations, including the cerebral accumulation of misfolded protein aggregates, neuroinﬂammation, synaptic dysfunction, and neuronal loss, along with behavioral impairments.
What’s Traumatic Brain Injury or TBI?
TBI represents a ubiquitous problem globally and could play a significant role in AD or CTE’s pathogenesis and etiology later in life. TBI events appear to trigger and exacerbate some of the pathological processes in these diseases, particularly the formation and accumulation of misfolded protein aggregates composed of amyloid-beta (ab) and tau. Here, we describe the relationship between repetitive mild TBI and the development of Ab and tau pathology in patients affected by AD or CTE based on epidemiological and pathological studies in human cases and a thorough overview of data obtained in experimental animal models.
The molecular footprint of TBI
TBI may initiate misfolded oligomeric species that may subsequently spread the pathology through a prion-like seeding process of protein misfolding.
The National Head Injury Foundation deﬁnes traumatic brain injury (TBI) as an “insult to the brain caused by an external force that may produce diminished or altered states of consciousness, which results in impaired cognitive abilities or physical functioning.” The World Health Organization estimates that 10 million people worldwide are affected by TBI per year, speciﬁcally costing Americans $57 billion. TBI is the leading cause of death or disability noted in industrialized cities and children and young adults. TBI reduces life expectancy by seven years.
Mild TBI (mTBI) is acknowledged as head insults that cause a brief state of altered consciousness resulting in 30 minutes of unconsciousness, yet most mTBIs do not result in loss of consciousness. The consequences of repetitive mild TBITBIBI) is a popular topic in research because war veterans and contact sports athletes (i.e., American football, boxing, hockey, soccer, etc.) with TBI experiences are linked with a recently deﬁned disease: chronic traumatic encephalopathy (CTE), formerly termed dementia pugilistica.
Though the particular type of lesions resulting from mTBI is highly variable, various factors may play an essential role in the consequences of the impact, including rotational acceleration and deceleration forces, ﬂuidic pulses from the lateral ventricles generating shearing forces, blow location, among others.
Who gets TBI?
Athletes and soldiers having CTE display an overlapping and broad range of abnormal behaviors emerging mid-life that ultimately result in psychological issues that lead to violence and/or suicide. Following a primary TBI insult, many secondary mechanisms take effect, causing cytopathogenesis and neurological changes within the brain, as indicated by an association with neurodegenerative diseases, cognitive struggles, seizures, sleep disorders, neuroendocrine disorders, and other complications.
These secondary mechanisms involve excitotoxicity, Ca2þ overload, mitochondrial dysfunction, reactive oxygen species, and inﬂammation. These cellular and biochemical alterations lead to synaptic dysfunction, axonal degeneration, and neuronal death; thereby, initiating cognitive impairments. Interestingly, autopsy brain samples from CTE-diagnosed athletes and military veterans and others afﬁliated with some form of TBI, from teen ages to ’80s, display massive accumulation of misfolded protein aggregates, mainly composed of tau and amyloid-beta (Ab).
Molecular expressions of TBI
Tau and Abeta inclusions are mostly known for their association with Alzheimer’s disease (AD), which is the most common form of dementia affecting elderly individuals. Neuroﬁbrillary tangles (NFTs) are formed by aggregates of hyper-phosphorylated tau protein (Tau). Tau is a microtubule-associated protein that has six isoforms differing by 3R or 4R binding repeats. Tau plays a vital role in axonal stabilization, neuronal development, and neuronal polarity. Ab is a 38e43 amino acid peptide produced by the cleavage of the amyloid precursor protein (APP) by b- and g-secretase. These proteins misfold and aggregate under pathological conditions, forming long ﬁbrillar polymers, which bind amyloid dies (e.g., Thioﬂavin S and Congo red), and have a high resistance cellular proteolytic degradation.
We hope this article helps you understand a bit more about the neuro-impact of Traumatic Brain Injury (TBI) at the brain’s molecular level.