Scientists identify mechanism that could contribute to problems in Alzheimer's

April 26, 2012

Scientists at the Gladstone Institutes have unraveled a process by which depletion of a specific protein in the brain contributes to the memory problems associated with Alzheimer's disease. These findings provide new insights into the disease's development and may lead to new therapies that could benefit the millions of people worldwide suffering from Alzheimer's and other devastating neurological disorders.

The study, led by Gladstone Investigator Jorge J. Palop, PhD, revealed that low levels of a protein, called Nav1.1, disrupt the electrical activity between . Such activity is crucial for healthy and memory. Indeed, the researchers found that restoring Nav1.1 levels in mice that were genetically modified to mimic key aspects of Alzheimer's disease (AD-mice) improved learning and and increased their lifespan. They report their findings in the April 27 issue of Cell, available online today.

"It is estimated that more than 30 million people worldwide suffer from Alzheimer's disease and that number is expected to rise dramatically in the near future," said Lennart Mucke, MD, who directs at Gladstone, an independent and nonprofit biomedical-research organization. "This research improves our understanding of the biological processes that underlie in this disease and could open the door for new therapeutic interventions."

The researchers' findings suggest that Nav1.1 levels in special regulatory called parvalbumin cells, or , are essential to generate healthy brain-wave activity—and that problems in this process contribute to cognitive decline in AD-mice and possibly in patients with Alzheimer's.

In the brain, neurons form highly interconnected networks, using chemical and electrical signals to communicate with each other. The researchers investigated whether this communication between neurons is disrupted in AD-mice, and if so, how this may affect the symptoms of Alzheimer's disease.

To study this, they performed electroencephalogram (EEG) recordings—a technique that detects abnormalities in the brain's electrical waves such as those found in patients with epilepsy. They found that similar abnormalities emerged during periods of reduced gamma-wave oscillations—a type of brain wave that is crucial to regulating .

"Like a conductor in an orchestra, PV cells regulate brain rhythms by precisely controlling excitatory brain activity," said Laure Verret, PhD, postdoctoral fellow and lead author. "We found that PV cells in patients with Alzheimer's and in AD-mice have low levels of the protein Nav1.1—likely contributing to PV cell dysfunction. As a consequence, AD-mice had abnormal brain rhythms. By restoring Nav1.1 levels, we were able to re-establish normal brain function."

Indeed, the scientists found that increasing Nav1.1 levels in PV cells improves brain wave activity, learning, memory and survival rates in AD-mice.

"Enhancing Nav1.1 activity, and consequently improving PV cell function, may help in the treatment of Alzheimer's disease and other neurological disorders associated with gamma-wave alterations and cognitive impairments such as epilepsy, autism and schizophrenia," said Dr. Palop, who is also an assistant professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "These findings may allow us to develop therapies to help patients with these devastating diseases."

Related Stories

Recommended for you

Alzheimer's Tau protein forms toxic complexes with cell membranes

November 22, 2017
The brains of patients with Alzheimer's disease contain characteristic tangles inside neurons. These tangles are formed when a protein called Tau aggregates into twisted fibrils. As a result, the neurons' transport systems ...

Researchers reveal new details on aged brain, Alzheimer's and dementia

November 21, 2017
In a comprehensive analysis of samples from 107 aged human brains, researchers at the Allen Institute for Brain Science, UW Medicine and Kaiser Permanente Washington Health Research Institute have discovered details that ...

Dementia study sheds light on how damage spreads through brain

November 20, 2017
Insights into how a key chemical disrupts brain cells in a common type of dementia have been revealed by scientists.

Researchers describe new biology of Alzheimer's disease

November 20, 2017
In a new study, researchers from Boston University School of Medicine (BUSM) describe a unique model for the biology of Alzheimer's disease (AD) which may lead to an entirely novel approach for treating the disease. The findings ...

Study shows video games could cut dementia risk in seniors

November 16, 2017
Could playing video games help keep the brain agile as we age?

New player in Alzheimer's disease pathogenesis identified

November 14, 2017
Scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) have shown that a protein called membralin is critical for keeping Alzheimer's disease pathology in check. The study, published in Nature Communications, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.