Researchers have recently developed a novel intervention strategy for specific neurodegenerative diseases, including Alzheimer’s disease (AD), built upon a deeper comprehension of disease mechanisms. The study was published in Science Translational Medicine.

Understanding AD and Neurodegenerative Diseases

AD is the most common cause of dementia. Protein deposits are the hallmark of AD and many other related neurodegenerative diseases. Deposit burden correlates well with disease progression in patients. The vast majority of these disease cases are sporadic and have no apparent obvious genetic cause. Elucidating the causes that lead to protein pathogenesis and neurodegeneration is critical for early diagnosis and intervention of AD and other related devastating diseases.

Therefore, rTBI is considered as a risk factor for such neurodegenerative diseases. However, until now the experimental evidence for a direct link has been lacking, and the underlying mechanisms have been unclear.

The study shows that rTBI not only promotes de novo tau pathogenesis, but also facilitates existing pathological tau transmission and spread in various mouse models.

Molecular Mechanism Behind rTBI-Induced Protein Pathogenesis Revealed

Specifically, the researchers demonstrated that axonal microtubule disruption is one of the molecular mechanisms underlying rTBI-induced protein pathogenesis and neurodegeneration. As a result, the researchers suggested that properly maintaining axonal microtubule stability, such as through a brain-penetrating microtubule-stabilizing compound, could reduce rTBI-induced microtubule damage, protein accumulation, tissue degeneration and behavioral deficits.