Elevating brain protein allays symptoms of Alzheimer's and improves memory

August 25, 2016, Salk Institute
In a mouse model of Alzheimer's disease, Salk Institute researchers show that raising levels of neuregulin-1 (right) lowers a marker of disease pathology in a part of the brain that controls memory compared with controls (left). Credit: Salk Institute

Boosting levels of a specific protein in the brain alleviates hallmark features of Alzheimer's disease in a mouse model of the disorder, according to new research published online August 25, 2016 in Scientific Reports.

The , called neuregulin-1, has many forms and functions across the brain and is already a potential target for brain disorders such as Parkinson's disease, and schizophrenia.

"Neuregulin-1 has broad therapeutic potential, but mechanistically, we are still learning about how it works," says the study's senior investigator Kuo-Fen Lee, a professor in the Salk Institute's Clayton Foundation Laboratories for Peptide Biology and holder of the Helen McLoraine Chair in Molecular Neurobiology. "We've shown that it promotes metabolism of the brain plaques that are characteristic of Alzheimer's disease."

Previously, researchers have shown that treating cells with neuregulin-1, for example, dampens levels of , a molecule that generates amyloid beta, which aggregate and form plaques in the brains of Alzheimer's patients. Other studies suggest that neuregulin-1 could protect neurons from damage caused by blockage of blood flow.

In the new study, Lee's team tested this idea in a mouse model of Alzheimer's disease by raising the levels of one of two forms of neuregulin-1 in the hippocampus, an area of the brain responsible for learning and memory. Both forms of the protein seemed to improve performance on a test of spatial memory in the models.

What's more, the levels of cellular markers of disease—including the levels of amyloid beta and plaques—were noticeably lower in mice with more neuregulin-1 compared to controls.

The group's experiments suggest that neuregulin-1 breaks up plaques by raising levels of an enzyme called neprilysin, shown to degrade . But that is probably not the only route through which neuregulin-1 confers its benefits, and the group is exploring other possible mechanisms—such as whether the protein improves signaling between neurons, which is impaired in Alzheimer's—says the study's first author Jiqing Xu, a research associate in Lee's group.

A neuregulin-1 treatment is not available on the market, though it is being explored in clinical trials as a potential treatment for and Parkinson's disease. One advantage of neuregulin-1 as a potential drug is that it can cross the blood brain barrier, which means that it could be administered relatively noninvasively even though the efficiency is not clear. On the other hand, other research suggests too much of the protein impairs function. Working with chemists at Salk, Lee's team has come up with a small molecule that can raise levels of existing neuregulin-1 (rather than administering it directly) and are testing it in cells. This alternative therapy could be a better way to prevent plaques from forming because small molecules more readily cross the .

The group is also interested in neuregulin-1 for its ties to schizophrenia. An alteration in the neuregulin-1 gene—a single change in one letter of the DNA code for the protein—has been found in families with schizophrenia and linked to late-onset Alzheimer's disease with psychosis. The protein may be a way to understand the overlap between Alzheimer's and other , Lee says.

An important caveat is that the new research was conducted in a single type of of Alzheimer's. Lee's group is testing neuregulin-1's affects across other models. "There's much more work ahead before neuregulin-1 could become a treatment, but we are excited about its potential, possibly in combination with other therapeutics for Alzheimer's disease," Lee says.

Explore further: Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

Related Stories

Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

June 29, 2016
Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's ...

Scientists reveal why people with the ApoE4 gene are more susceptible to Alzheimer's disease

August 17, 2016
For decades, scientists have known that people with two copies of a gene called apolipoprotein E4 (ApoE4) are much more likely to have Alzheimer's disease at age 65 than the rest of the population. Now, researchers at the ...

Genetically engineered mice suggest new model for how Alzheimer's causes dementia

July 4, 2016
Using a novel, newly developed mouse model that mimics the development of Alzheimer's disease in humans, Johns Hopkins researchers say they have been able to determine that a one-two punch of major biological "insults" must ...

'Pac-Man' gene implicated in Alzheimer's disease

July 26, 2016
A gene that protects the brain from the harmful build-up of amyloid-beta, one of the causative proteins implicated in Alzheimer's disease, has been identified as a new target for therapy by NeuRA researchers.

Immune cells may protect against Alzheimer's

May 19, 2016
Clusters of immune cells in the brain previously associated with Alzheimer's actually protect against the disease by containing the spread of damaging amyloid plaques, a new Yale University School of Medicine study shows.

Promising new methods for early detection of Alzheimer's disease

July 8, 2016
New methods to examine the brain and spinal fluid heighten the chance of early diagnosis of Alzheimer's disease. Results from a large European study, led by researchers at the Karolinska Institutet, are now published in the ...

Recommended for you

Researchers classify Alzheimer's patients in six subgroups

December 5, 2018
Researchers studying Alzheimer's disease have created an approach to classify patients with Alzheimer's disease, a finding that may open the door for personalized treatments.

Neuroscientists pinpoint genes tied to dementia

December 3, 2018
A UCLA-led research team has identified genetic processes involved in the neurodegeneration that occurs in dementia—an important step on the path toward developing therapies that could slow or halt the course of the disease. ...

Detecting signs of neurodegeneration earlier and more accurately

November 30, 2018
Signs of neurodegenerative diseases, appearing years before the emergence of clinical manifestations, can be detected during the examination of medical samples by means of fluorescence microscopy by using new sensitive and ...

Never-before-seen DNA recombination in the brain linked to Alzheimer's disease

November 21, 2018
Scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified gene recombination in neurons that produces thousands of new gene variants within Alzheimer's disease brains. The study, published today ...

New information on the pathological mechanisms of Alzheimer's disease

November 21, 2018
Researchers at the University of Helsinki have discovered a mechanism by which harmful tau protein aggregates are transmitted between neurons. Alongside amyloid plaques, tau aggregates in the brain are a significant factor ...

DNA vaccine reduces both toxic proteins linked to Alzheimer's

November 20, 2018
A DNA vaccine tested in mice reduces accumulation of both types of toxic proteins associated with Alzheimer's disease, according to research that scientists say may pave the way to a clinical trial.

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.