Traumatic Brain Injury as a Risk Factor for Alzheimer’s Disease and Potential for Pathogenetic Therapy

• Published in: Neuroscience and behavioral physiology 2024-05, Vol.54 (4), p.593-602
• Main Authors: Litvinenko, I. V., Naumov, K. M., Lobzin, V. Yu, Emelin, A. Yu, Dynin, P. S., Kolmakova, K. A., Nikishin, V. O.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Aquaporin 4; Arteries; Behavioral Sciences; Biomedical and Life Sciences; Biomedicine; Blood flow; Blood-brain barrier; Cerebral blood flow; Dementia disorders; Energy metabolism; Inflammation; Membrane permeability; Metabolism; Neurobiology; Neurodegenerative diseases; Neuronal-glial interactions; Neurosciences; Permeability; Protein transport; Protein turnover; Reviews; Risk factors; Tau protein; Traumatic brain injury; Vascular dementia; β-Amyloid
• ISSN: 0097-0549; 1573-899X
• DOI: 10.1007/s11055-024-01632-8

This article examines the role of traumatic brain injury as a trigger for the development of neurodegenerative changes. Dysfunction of neurovascular units and disruption of the functional and compensatory capabilities of blood flow are addressed. The importance of microhemorrhages in the acute period of traumatic brain injury (TBI) and the formation of neuroinflammation is emphasized. Mitochondrial dysfunction has been noted to play a role in increasing the risk of developing Alzheimer’s disease (AD) in patients with TBI. Decreased expression of tight junction proteins leads to increased permeability of the blood–brain barrier (BBB). TBI, provoking endothelial dysfunction, contributes to disrupting β-amyloid and tau protein metabolism and aggravating vascular damage, which results in a vicious circle which can lead to the development of AD and dementia. Changes in the cerebral arteries leading to impairment of interstitial fluid transport are seen as an important part of the “amyloid cascade” on the background of genetically mediated disorders of glial membranes associated with defects in aquaporin-4. The TBI-triggered reaction cascade includes all the main elements of the pathogenesis of AD: disturbances in energy metabolism, microcirculation, and clearance of metabolic products, which leads to the accumulation of amyloid protein in the brain with the subsequent development of tauopathy. Cerebrolysin modulates the permeability of the BBB, blocking the development of neuroinflammation; it reduces the accumulation of pathological forms of proteins and can slow the progression of neurodegeneration.