Inflammatory mediator enhances plaque formation in Alzheimer's disease

September 7, 2011

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that causes progressive cognitive impairment and memory loss. Now, a new study published by Cell Press in the September 8 issue of the journal Neuron identifies a previously unrecognized link between neuroinflammation and the classical pathological brain changes that are the hallmark of the disease. In addition, the research identifies a new potential therapeutic target for AD.

AD is characterized by abnormal accumulation of amyloid Β (AΒ) protein plaques and neurofibrillary tangles of tau protein in the brain. In addition to these classical hallmarks, neuroinflammation has also been identified as a major component of the disease. Previous research has suggested that AD associated inflammation increases the inducible nitric oxide synthase (NOS2) in and support cells. Importantly, NOS2 leads to generation of nitric oxide (NO) which has been linked with neurodegeneration.

"One of the fingerprints of NO is tyrosine nitration, a posttranslational protein modification that can induce structural changes leading to protein aggregation," explains senior study author, Dr. Michael T. Heneka, from the University of Bonn in Germany. "Since there is so far no mechanistic explanation how expression of NOS2 and the subsequent production of NO and its reaction products modulate AΒ and thereby the progression of AD, we speculated that nitration of AΒ might contribute to AD pathology."

In their study, first author Dr. Markus P. Kummer and colleagues discovered that AΒ is a novel NO target. They observed nitrated AΒ in AD and AD mouse models and found that this modification accelerated the deposition of human AΒ. Importantly, reduction of NOS2 reduced AΒ deposition and memory deficits in a mouse model of AD. Further, nitrated AΒ induced the formation of amyloid plaques when injected into the brains of mice with genetic mutations associated with AD.

"Taken together, our results identify a novel modification of AΒ, tyrosine nitration, and propose a causative link between the AΒ cascade, activation of NOS2, and the subsequent increase in its reaction product during AD," concludes Dr. Heneka. "We think that nitrated AΒ may serve as marker of early AΒ plaque formation. More importantly, it may be a promising target for an AD therapy, and that application of specific inhibitors of NOS2 may therefore open a new therapeutic avenue in AD."

Related Stories

Recommended for you

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

New study reveals contrasts in how groups of neurons function during decision making

July 19, 2017
By training mice to perform a sound identification task in a virtual reality maze, researchers at Harvard Medical School and the Istituto Italiano di Tecnologia (IIT) have identified striking contrasts in how groups of neurons ...

Healthy heart in 20s, better brain in 40s?

July 19, 2017
Folks with heart-healthy habits in their 20s tend to have larger, healthier brains in their 40s—brains that may be better prepared to withstand the ravages of aging, a new study reports.

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.