Featured Research

from universities, journals, and other organizations

Why don’t we all get Alzheimer's disease?

Date:
August 7, 2013
Source:
University of California, San Diego Health Sciences
Summary:
Scientists offer an explanation for why we all don't get Alzeimer's disease. Though one might think the brains of people who develop Alzheimer’s disease possess building blocks of the disease absent in healthy brains, for most sufferers, this is not true.

Top: Vesicles containing APP (green) and BACE (red) are normally segregated in neurons. Bottom: After neuronal stimulation, known to produce more beta-amyloid, APP and BACE converge in common vesicles, depicted in yellow.
Credit: UC San Diego School of Medicine

Though one might think the brains of people who develop Alzheimer's disease (AD) possess building blocks of the disease absent in healthy brains, for most sufferers, this is not true. Every human brain contains the ingredients necessary to spark AD, but while an estimated 5 million Americans have AD -- a number projected to triple by 2050 -- the vast majority of people do not and will not develop the devastating neurological condition.

For researchers like Subhojit Roy, MD, PhD, associate professor in the Departments of Pathology and Neurosciences at the University of California, San Diego School of Medicine, these facts produce a singular question: Why don't we all get Alzheimer's disease?

In a paper published in the August 7 issue of the journal Neuron, Roy and colleagues offer an explanation -- a trick of nature that, in most people, maintains critical separation between a protein and an enzyme that, when combined, trigger the progressive cell degeneration and death characteristic of AD.

"It's like physically separating gunpowder and match so that the inevitable explosion is avoided," said principal investigator Roy, a cell biologist and neuropathologist in the Shiley-Marcos Alzheimer's Disease Research Center at UC San Diego. "Knowing how the gunpowder and match are separated may give us new insights into possibly stopping the disease."

The severity of AD is measured in the loss of functioning neurons. In pathological terms, there are two tell-tale signs of AD: clumps of a protein called beta-amyloid "plaques" that accumulate outside neurons and threads or "tangles" of another protein, called tau, found inside neurons. Most neuroscientists believe AD is caused by the accumulating assemblies of beta-amyloid protein triggering a sequence of events that leads to impaired cell function and death. This so-called "amyloid cascade hypothesis" puts beta-amyloid protein at the center of AD pathology.

Creating beta-amyloid requires the convergence of a protein called amyloid precursor protein (APP) and an enzyme that cleaves APP into smaller toxic fragments called beta-secretase or BACE.

"Both of these proteins are highly expressed in the brain," said Roy, "and if they were allowed to combine continuously, we would all have AD."

But that doesn't happen. Using cultured hippocampal neurons and tissue from human and mouse brains, Roy -- along with first author Utpal Das, a postdoctoral fellow in Roy's lab, and colleagues -- discovered that healthy brain cells largely segregate APP and BACE-1 into distinct compartments as soon as they are manufactured, ensuring the two proteins do not have much contact with each other.

"Nature seems to have come up with an interesting trick to separate co-conspirators," said Roy.

The scientists also found that the conditions promoting greater production of beta-amyloid protein boost the convergence of APP and BACE. Specifically, an increase in neuronal electrical activity -- known to increase the production of beta-amyloid -- also led to an increase in APP-BACE convergence. Post-mortem examinations of AD patients revealed increased physical proximity of the proteins as well, adding support to the pathophysiological significance of this phenomenon in human disease.

Das said the findings are fundamentally important because they elucidate some of the earliest molecular events triggering AD and show how a healthy brain naturally avoids them. In clinical terms, they point to a possible new avenue for ultimately treating or even preventing the disease.

"An exciting aspect is that we can perhaps screen for molecules that can physically keep APP and BACE-1 apart," said Das. "It's a somewhat unconventional approach."


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Utpal Das, DavidA. Scott, Archan Ganguly, EdwardH. Koo, Yong Tang, Subhojit Roy. Activity-Induced Convergence of APP and BACE-1 in Acidic Microdomains via an Endocytosis-Dependent Pathway. Neuron, 2013; 79 (3): 447 DOI: 10.1016/j.neuron.2013.05.035

Cite This Page:

University of California, San Diego Health Sciences. "Why don’t we all get Alzheimer's disease?." ScienceDaily. ScienceDaily, 7 August 2013. <www.sciencedaily.com/releases/2013/08/130807133434.htm>.
University of California, San Diego Health Sciences. (2013, August 7). Why don’t we all get Alzheimer's disease?. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2013/08/130807133434.htm
University of California, San Diego Health Sciences. "Why don’t we all get Alzheimer's disease?." ScienceDaily. www.sciencedaily.com/releases/2013/08/130807133434.htm (accessed October 23, 2014).

Share This



More Mind & Brain News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Working Mother Getaway: Beaches Turks & Caicos

Working Mother Getaway: Beaches Turks & Caicos

Working Mother (Oct. 22, 2014) Feast your eyes on this gorgeous family-friendly resort. Video provided by Working Mother
Powered by NewsLook.com
What Your Favorite Color Says About You

What Your Favorite Color Says About You

Buzz60 (Oct. 22, 2014) We all have one color we love to wear, and believe it or not, your color preference may reveal some of your character traits. In celebration of National Color Day, Krystin Goodwin (@kyrstingoodwin) highlights what your favorite colors may say about you. Video provided by Buzz60
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
Portable Breathalyzer Gets You Home Safely

Portable Breathalyzer Gets You Home Safely

Buzz60 (Oct. 21, 2014) Breeze, a portable breathalyzer, gets you home safely by instantly showing your blood alcohol content, and with one tap, lets you call an Uber, a cab or a friend from your contact list to pick you up. Sean Dowling (@SeanDowlingTV) has the details. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins