Boosting a gene in brain helper cells slows Alzheimer's progression

Increasing the expression of a gene in cells that help neurons in the brain protects neurons in a mouse model of Alzheimer's disease

The findings come from a new study published Jan.

The research was led by Professor Jeffrey Johnson of the UW-Madison School of Pharmacy and his collaborators at the University of Edinburgh in Scotland

Researchers have previously identified Nrf2 as a therapeutic target for Parkinson's disease and amyotrophic lateral sclerosis (ALS)

A team led by the University of Wisconsin-Madison found that increasing levels of Nrf2 in a type of supporting cells called astrocytes helped neurons greatly reduce the accumulation of two disordered proteins at the heart of Alzheimer's disease

These proteins, tau and beta-amyloid, form dangerous clumps called tangles and plaques, respectively

Mice overexpressing Nrf2 performed better on memory and physical tests

"The magnitude of the reduction in beta-amyloid and tau and the almost complete reversal of the genetic changes were remarkable," Johnson said

Nrf2 controls the expression of many genes that protect the body from damage such as oxidative stress or inflammation

To investigate how persistent activation of Nrf2 in astrocytes protects the brain, Johnson's lab bred mice to over-accumulate beta-amyloid around neurons to mimic Alzheimer's disease, and A large amount of Nrf2 is expressed in astrocytes

Compared with mice that didn't boost Nrf2, those mice with a high amount of the Nrf2 gene had almost 90 percent less beta-amyloid in their brains

In mice and humans, a symptom of Alzheimer's is memory loss

Giles Hardingham and his team at the University of Edinburgh conducted similar experiments in mice that had accumulated too much tau

"Nrf2 overexpression had very similar effects in both tau and beta-amyloid models," Hardingham said

The team suspects that Nrf2 increases the ability of neurons to digest these proteins, thereby clearing them

While Nrf2 is an attractive candidate for anti-Alzheimer's treatment, it has been shown in the past to be difficult to activate in the brain using drugs

Another key factor in developing effective treatments for Alzheimer's is diagnosing patients earlier
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Researchers have found that Alzheimer's disease takes many years, if not decades, to fully develop
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Treating patients early may improve their prognosis
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"The new diagnostic tools that are currently being developed will be very useful," Johnson said
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