Alzheimer's precursor protein controls its own fate, study finds

April 10, 2012, University of South Florida
This is a microscopic image showing co-localization of a fragment of the amyloid precursor protein, known as sAPP-α, with BACE1, an enzyme involved in the development of characteristic Alzheimer's amyloid deposits. This merging suggests sAPP-α may serve as a mechanism to inhibit BACE1 activity and thus lower production of toxic amyloid beta associated with Alzheimer's disease. Credit: © University of South Florida

A research team led by the University of South Florida Department of Psychiatry & Behavioral Neurosciences has found that a fragment of the amyloid precursor protein (APP) -- known as sAPP-α and associated with Alzheimer's disease -- appears to regulate its own production. The finding may lead to ways to prevent or treat Alzheimer's disease by controlling the regulation of APP.

Their study is published online today in .

"The purpose of this study was to help better understand why, in most cases of , the processing of APP becomes deregulated, which leads to the formation of deposits and neuron loss," said study senior author Dr. Jun Tan, professor of and the Robert A. Silver Chair, Rashid Laboratory for Developmental Neurobiology at the USF Silver Child Development Center. "The many risk factors for Alzheimer's disease can change the way APP is processed, and these changes appear to promote plaque formation and neuron loss."

An estimated 30 million people worldwide and 5 million in the U.S. have Alzheimer's. With the aging of the "Baby Boom" generation, the prevalence of the debilitating disease is expected to increase dramatically in the U.S. in the coming years. Currently, there are no disease-modifying treatments to prevent, reverse or halt the progression of Alzheimer's disease, only medications that may improve symptoms for a short time.

"For the first time, we have direct evidence that a secreted portion of APP itself, so called 'sAPP-α,' acts as an essential stop-gap mechanism," said the study's lead author Dr. Demian Obregon, a resident specializing in research in the Department of Psychiatry & Behavioral Neurosciences at USF Health. "Risk factors associated with Alzheimer's disease lead to a decline in sAPP-α levels, which results in excessive activity of a key enzyme in Aβ formation,"

In initial studies using cells, and in follow-up studies using mice genetically engineered to mimic Alzheimer's disease, the investigators found that the neutralization of sAPP-α leads to enhanced Aβ formation. This activity depended on sAPP-α's ability to associate with the APP-converting enzyme, BACE1. When this interaction was blocked, Aβ formation was restored.

The authors suggest that through monitoring and correcting low sAPP-α levels, or through enhancing its association with BACE, Alzheimer's disease may be prevented or treated.

Explore further: Autism may be linked to abnormal immune system characteristics and novel protein fragment

Related Stories

Autism may be linked to abnormal immune system characteristics and novel protein fragment

January 3, 2012
Immune system abnormalities that mimic those seen with autism spectrum disorders have been linked to the amyloid precursor protein (APP), reports a research team from the University of South Florida's Department of Psychiatry ...

New biomarker may help with early diagnosis of Alzheimer's disease

June 22, 2011
A new biomarker may help identify which people with mild memory deficits will go on to develop Alzheimer's disease, according to a new study published in the June 22, 2011, online issue of Neurology, the medical journal of ...

Characterizing a toxic offender

December 9, 2011
The brains of individuals with Alzheimer's disease contain protein aggregates called plaques and tangles, which interfere with normal communication between nerve cells and cause progressive learning and memory deficits. Now, ...

Road block as a new strategy for the treatment of Alzheimer's

August 22, 2011
Blocking a transport pathway through the brain cells offers new prospects to prevent the development of Alzheimer's. Wim Annaert and colleagues of VIB and K.U. Leuven discovered that two main agents involved in the inception ...

Recommended for you

Alzheimer's disease: Neuronal loss very limited

January 17, 2018
Frequently encountered in the elderly, Alzheimer's is considered a neurodegenerative disease, which means that it is accompanied by a significant, progressive loss of neurons and their nerve endings, or synapses. A joint ...

Anxiety: An early indicator of Alzheimer's disease?

January 12, 2018
A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of ...

One of the most promising drugs for Alzheimer's disease fails in clinical trials

January 11, 2018
To the roughly 400 clinical trials that have tested some experimental treatment for Alzheimer's disease and come up short, we can now add three more.

Different disease types associated with distinct amyloid-beta prion strains found in Alzheimer's patients

January 9, 2018
An international team of researchers has found different disease type associations with distinct amyloid-beta prion strains in the brains of dead Alzheimer's patients. In their paper published in Proceedings of the National ...

Advances in brain imaging settle debate over spread of key protein in Alzheimer's

January 5, 2018
Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer's disease - and hence that blocking its spread ...

Molecular mechanism behind HIV-associated dementia revealed

January 5, 2018
For the first time, scientists have identified and inhibited a molecular process that can lead to neurodegeneration in patients with HIV, according to a Northwestern Medicine 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.