Repeated Mild Traumatic Brain Injuries and Increased Dementia Risk: A Pilot Study Investigating Cerebral Amyloid Angiopathy as a Mechanistic Link

Abstract

Traumatic brain injury (TBI) is estimated to affect ~69 million people worldwide each year. Mild TBI’s are the most common form of brain injury, characterized by little-to-no time unconscious and minimal observable deficits immediately post-injury. Mild brain injuries are commonly attributed to participation in contact sports and military service. Even mild TBIs, especially repeated injuries, have devastating long-term consequences, including an increased risk of stroke and dementia. Therefore, it is of great interest to determine the mechanisms that drive the relationship between different types of TBIs and various aspects of dementia-associated neuropathology, so that targets for intervention may be identified. Repetitive mild TBIs are most notably associated with chronic traumatic encephalopathy (CTE; a tauopathy), though some evidence suggests they may also contribute to Alzheimer’s disease and other neurodegenerative conditions. On the other hand, less is known about whether cerebral amyloid angiopathy (CAA) may also be a mechanism linking TBI to dementia. CAA is the accumulation of amyloid protein (most commonly beta-amyloid, associated with Alzheimer's disease) within the cerebral vasculature, contributing to increased risk of dementia [both vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease], as well as ischemic and hemorrhagic stroke. Increased levels of CAA are observed in former athletes, who tend to have a history of repetitive mild brain injuries; however, animal studies are needed to experimentally determine whether and how repetitive mild TBIs influence the initiation and progression of CAA and related pathologies. Current work will be investigating this link between repetitive mild TBI and CAA progression in mice. Our long-term goal is to identify mechanisms linking TBI and increased dementia risk, which may in turn reveal novel targets for treatment.

Faculty Sponsors

Dr. Lisa Robinson, Dr. William Kochen, Dr. Robert Speth, Dr. Benedict C. Albensi

Project Type

Event

Location

Alvin Sherman Library

Start Date

4-5-2023 12:00 PM

End Date

4-6-2023 4:00 PM

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Repeated Mild Traumatic Brain Injuries and Increased Dementia Risk: A Pilot Study Investigating Cerebral Amyloid Angiopathy as a Mechanistic Link

Alvin Sherman Library

Traumatic brain injury (TBI) is estimated to affect ~69 million people worldwide each year. Mild TBI’s are the most common form of brain injury, characterized by little-to-no time unconscious and minimal observable deficits immediately post-injury. Mild brain injuries are commonly attributed to participation in contact sports and military service. Even mild TBIs, especially repeated injuries, have devastating long-term consequences, including an increased risk of stroke and dementia. Therefore, it is of great interest to determine the mechanisms that drive the relationship between different types of TBIs and various aspects of dementia-associated neuropathology, so that targets for intervention may be identified. Repetitive mild TBIs are most notably associated with chronic traumatic encephalopathy (CTE; a tauopathy), though some evidence suggests they may also contribute to Alzheimer’s disease and other neurodegenerative conditions. On the other hand, less is known about whether cerebral amyloid angiopathy (CAA) may also be a mechanism linking TBI to dementia. CAA is the accumulation of amyloid protein (most commonly beta-amyloid, associated with Alzheimer's disease) within the cerebral vasculature, contributing to increased risk of dementia [both vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease], as well as ischemic and hemorrhagic stroke. Increased levels of CAA are observed in former athletes, who tend to have a history of repetitive mild brain injuries; however, animal studies are needed to experimentally determine whether and how repetitive mild TBIs influence the initiation and progression of CAA and related pathologies. Current work will be investigating this link between repetitive mild TBI and CAA progression in mice. Our long-term goal is to identify mechanisms linking TBI and increased dementia risk, which may in turn reveal novel targets for treatment.