Study Suggests Disruption of Circadian Clock May Aid Alzheimer's Treatment

Under the leadership of Erik Musiek, MD, PhD, and first author Jiyeon Lee, PhD, the research team focused on whether inhibiting a particular circadian clock protein could slow neurodegenerative progression. Their findings show that blocking this protein reduces levels of tau, a harmful protein linked to Alzheimer's, and minimizes damage to brain tissue.

The protein in question, REV-ERBα, plays a role in regulating daily rhythms of metabolism and inflammation. Although its function in the brain remains less understood, prior research has indicated that REV-ERBα affects levels of nicotinamide adenine dinucleotide (NAD+), an essential molecule for metabolism, energy production, and DNA repair. Reduced NAD+ levels are often associated with brain aging and neurodegenerative diseases. Many supplements aim to enhance NAD+ levels as a means to combat aging and promote cellular health.

To investigate REV-ERBα’s impact, the team genetically deleted the protein in two groups of mice: one group saw the loss throughout the body, while the other experienced removal only in astrocytes—glial cells key to central nervous system support. In both scenarios, NAD+ levels substantially increased, suggesting that removing REV-ERBα in astrocytes could directly elevate NAD+ levels in the brain, pointing to a promising direction for future neurodegeneration treatments.

Further experiments involved blocking REV-ERBα using genetic methods and a novel drug already showing potential in amyloid-β and Parkinson's disease research. This approach resulted in increased NAD+ levels and protection against tau-related brain damage, with tau aggregates known to impair brain function and contribute to neurodegenerative diseases like Alzheimer's.

Overall, the study indicates that manipulating the internal clock by inhibiting REV-ERBα could offer a new strategy to preserve brain health, prevent tau accumulation, and potentially slow the progression of Alzheimer's disease.