**Could Disrupting Your Internal Clock Be the Key to Treating Alzheimer’s?**

A surprising new study published in the journal *Nature Aging* suggests that using drugs to target the circadian protein REV-ERBα could potentially slow the progression of Alzheimer’s disease.

In the early stages of Alzheimer’s, proteins like amyloid and tau build up in parts of the medial temporal lobe — a brain region essential for memory formation. This buildup causes previously healthy neurons to die off, leading to brain shrinkage.

According to co-author Erik Museik, MD, PhD, more than half of the 82 genes associated with Alzheimer’s risk are controlled by the circadian rhythm. Museik’s team believes that this correlation could offer valuable insights into developing therapeutic treatments that might slow—or even stop—the progression of the disease.

### Exploring the Role of REV-ERBα

In the study, researchers experimented on two groups of mice. In the first group, they removed the circadian protein entirely. In the second group, they deleted the protein from astrocytes—the neuron-support cells that make up our brains and spinal cords.

Two important outcomes emerged from this approach:

1. **Blocking REV-ERBα increased levels of NAD+**, a coenzyme linked to healthy brain aging that previous research suggests could improve cognitive function.

2. **Inhibiting REV-ERBα and increasing NAD+ protected mice from tau buildup**, a hallmark of Alzheimer’s disease.

These findings provide promising evidence that a drug suppressing REV-ERBα might offer hope in treating Alzheimer’s.

### Alzheimer’s and the Circadian Rhythm: A Cyclical Relationship

Another study led by Museik, published in *Nature Neuroscience* in October, further supports the theory that Alzheimer’s could be linked to disruptions in our circadian rhythm.

The paper highlights that Alzheimer’s symptoms often follow a cyclical pattern. Many people living with Alzheimer’s experience altered sleep cycles, such as napping throughout the day and feeling more alert at night.

To better understand this phenomenon, the research team studied gene expression in mice with amyloid protein accumulation, simulating “early stage” Alzheimer’s. They discovered that this buildup disrupted the rhythm of hundreds of proteins in the brain more severely than typical aging alone.

While amyloid buildup didn’t completely “switch off” genes, it caused them to fire sporadically and less effectively—potentially harming brain health. For instance, some affected genes regulate microglia, the brain’s “clean-up crew” cells responsible for breaking down waste, including excess amyloid. When these genes become less effective, amyloid accumulates further, inhibiting the genes even more—a domino effect driving neurodegeneration.

### New Rhythms and Neuroinflammation

The *Nature Neuroscience* study also found that amyloid buildup generated new rhythms in genes that normally do not cycle. These changes are significant and may worsen cognitive decline.

Notably, these new rhythms impact genes responsible for inflammation, potentially leading to excess inflammation in nervous tissue—known as neuroinflammation. This condition can cause symptoms such as brain fog and memory loss.

### Looking Ahead

While these studies offer breakthrough insights into the role of the circadian rhythm in Alzheimer’s progression, much remains to be learned. Researchers are hopeful that targeting the internal clock could become a key strategy in developing effective treatments for this devastating disease.

Stay tuned as science continues to unravel the complex relationship between our internal clocks and brain health.
https://www.popularmechanics.com/science/health/a69204640/circadian-rhythm-alzheimers-breakthrough/