Glaucoma medication could help prevent the buildup of Alzheimer’s-related tau proteins.
A common glaucoma medication has shown potential to prevent the accumulation of tau proteins linked to Alzheimer’s and other forms of dementia in studies on zebrafish and mice. Researchers from the UK Dementia Research Institute at the University of Cambridge screened over 1,400 clinically approved drugs on genetically modified zebrafish to identify those capable of reducing tau build-up. They found that carbonic anhydrase inhibitors, including the glaucoma drug methazolamide, were effective in clearing tau aggregates and mitigating disease signs in both zebrafish and mice carrying tau mutations that cause human dementias.
Tauopathies, such as Alzheimer’s disease and chronic traumatic encephalopathy, are characterized by tau protein accumulation within brain cells. Unlike conventional cell culture testing, using zebrafish offers a more accurate representation of tau-related diseases in living organisms and enables high-throughput drug screening. Methazolamide works by inhibiting carbonic anhydrase, an enzyme involved in cellular acidity regulation. This action encourages the lysosomes—cells’ waste disposal units—to move tau proteins to the cell surface for expulsion.
When tested on genetically modified mice with tau accumulation, methazolamide improved cognitive function and reduced tau aggregates compared to untreated mice. The research team noted that methazolamide’s established safety profile could expedite clinical trials, advancing the potential to repurpose this drug for treating tau-related neurodegenerative diseases.
This study highlights the effectiveness of zebrafish models in exploring new uses for existing drugs, which could accelerate the development of treatments for diseases such as Huntington’s and Parkinson’s, also associated with protein aggregates. Supported by the UK Dementia Research Institute, the Tau Consortium, and Wellcome, the research marks a promising step toward combatting tauopathy-linked neurodegeneration.