PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

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

2013-08-07
(Press-News.org) 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."



INFORMATION:

Co-authors are David Scott, Archan Ganguly and Yong Tang, UCSD Departments of Pathology and Neurosciences; and Edward H. Koo, UCSD Department of Neurosciences. Roy and Koo are also members of the Shiley-Marcos Alzheimer's Disease Research Center (ADRC) at UC San Diego.

Funding for this research came from the American Federation for Aging Research, National Institutes of Health grant P50AG005131 and a gift from Darlene Shiley to the ADRC.



ELSE PRESS RELEASES FROM THIS DATE:

The odd couple

2013-08-07
This image was taken by the Very Large Telescope (VLT) at ESO's Paranal Observatory in Chile — the best place in the southern hemisphere for astronomical observing. But even without the help of telescopes like the VLT, a glance towards the southern constellation of Dorado (The Swordfish or Dolphinfish [1]) on a clear, dark night reveals a blurry patch which, at first sight, appears to be just like a cloud in the Earth's atmosphere. At least, this may have been explorer Ferdinand Magellan's first impression during his famous voyage to the southern hemisphere in 1519. Although ...

A 'rocking' receptor: Crucial brain-signaling molecule requires coordinated motion to turn on

2013-08-07
Johns Hopkins biophysicists have discovered that full activation of a protein ensemble essential for communication between nerve cells in the brain and spinal cord requires a lot of organized back-and-forth motion of some of the ensemble's segments. Their research, they say, may reveal multiple sites within the protein ensemble that could be used as drug targets to normalize its activity in such neurological disorders as epilepsy, schizophrenia, Parkinson's and Alzheimer's disease. A summary of the results, published online in the journal Neuron on Aug. 7, shows that ...

Scripps Research Institute scientists find key signal that guides brain development

2013-08-07
LA JOLLA, CA – August 7, 2013 – Scientists at The Scripps Research Institute (TSRI) have decoded an important molecular signal that guides the development of a key region of the brain known as the neocortex. The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans and is responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness and other functions. "The mammalian neocortex has a distinctive structure featuring six layers of neurons, and our finding helps explain how this ...

Psychological adaptation to urbanization, technology reflected in word usage over last 200 years

2013-08-07
New research shows that as culture has evolved over the last two centuries – with increasing urbanization, greater reliance on technology, and widespread availability of formal education – so has human psychology. The findings are forthcoming in Psychological Science, a journal of the Association for Psychological Science. "This research shows that there has been a two-century long historical shift towards individualistic psychological functioning adapted to an urban environment and away from psychological functioning adapted to a rural environment," says psychological ...

Changes in language and word use reflect our shifting values, UCLA psychologist reports

2013-08-07
A new UCLA analysis of words used in more than 1.5 million American and British books published between 1800 and 2000 shows how our cultural values have changed. The increase or decrease in the use of certain words over the past two centuries — a period marked by growing urbanization, greater reliance on technology and the widespread availability of formal education — reveals how human psychology has evolved in response to major historical shifts, said Patricia Greenfield, a distinguished professor of psychology at UCLA and the author of the study. For instance, ...

AAAS report shows steady escalation of destruction in Aleppo

2013-08-07
In Syria's largest city, Aleppo, damage to buildings and infrastructure steadily increased over a ten-month period ending in May 2013, according to a new analysis by AAAS of high-resolution satellite images. Virtually all of the destruction appears to be in rebel-controlled or contested areas, and a substantial amount is in Aleppo's Ancient City, a UNESCO World Heritage Site. Aleppo has been the site of ongoing conflict since July 2012. Since then, the city has experienced a nearly constant rate of damage to its physical structures, at about three incidents per day on ...

The team of proteins that could have implications for the fight against cancer

2013-08-07
Researchers at Warwick Medical School have identified the key role played by a team of proteins in the process of mitosis. Working out how to control them may give scientists a way to destroy cancerous cells. The study, led by Professor Steve Royle and published in The Journal of Cell Biology, highlights the role of a newly identified team of proteins, TACC3-ch-TOG-clathrin, in forming inter-microtubule bridges that stabilise the kinetochore fibres (K-fibres) used in mitosis. When a cell divides, it produces a mitotic spindle which then makes sure that the chromosomes ...

Brain activation when processing Chinese hand-radicals

2013-08-07
A number of studies in which patients with lesions to frontal pre-motor areas are included have identified deficits in action comprehension. In addition, imaging studies have revealed the activation of brain areas associated with perception or action during tasks involving reading of words with related semantic meaning. For example, the mere passive reading of action verbs such as kick, pick and lick has been found to activate areas of the sensory-motor cortex associated with the legs, hands and face, respectively. To investigate the semantic processing of Chinese radicals ...

Mechanism underlying cisplatin-induced ototoxicity

2013-08-07
Studies have shown that calpain participates in gentamicin-, neomycin- and kanamycin-induced inner ear cell apoptosis. Cisplatin has been shown to be an anticancer drug. However, cisplatin can lead to severe ototoxicity, induce cochlear cell apoptosis, and result in hearing decrease or loss, which limits the application of cisplatin in a clinical setting to a certain degree. A recent study by Liang Chang and colleagues from Jinzhou Central Hospital established a BALB/c mouse model of cisplatin-induced ototoxicity to detect the susceptibility to cisplatin-induced ototoxicity. ...

Caffeine 'traffic light': Do you want to know how much caffeine is in your drink?

2013-08-07
A team of researchers led by Prof. Young-Tae Chang from National University of Singapore and Prof. Yoon-Kyoung Cho from Ulsan National Institute of Science and Technology (UNIST), Korea, developed a fluorescent caffeine detector and a detection kit that lights up like a traffic light when caffeine is present in various drinks and solutions. The research work was published in Scientific Reports (Nature Publishing Group) on July 23, 2013. Caffeine drinks are ubiquitous and it would be unimaginable for many of us to go a day without caffeine. But certainly one begins to ...

LAST 30 PRESS RELEASES:

Intra-arterial tenecteplase for acute stroke after successful endovascular therapy

Study reveals beneficial microbes that can sustain yields in unfertilized fields

Robotic probe quickly measures key properties of new materials

Climate change cuts milk production, even when farmers cool their cows

Frozen, but not sealed: Arctic Ocean remained open to life during ice ages

Some like it cold: Cryorhodopsins

Demystifying gut bacteria with AI

Human wellbeing on a finite planet towards 2100: new study shows humanity at a crossroads

Unlocking the hidden biodiversity of Europe’s villages

Planned hydrogen refuelling stations may lead to millions of euros in yearly losses

Planned C-sections increase the risk of certain childhood cancers

Adults who have survived childhood cancer are at increased risk of severe COVID-19

Drones reveal extreme coral mortality after bleaching

New genetic finding uncovers hidden cause of arsenic resistance in acute promyelocytic leukemia

Native habitats hold the key to the much-loved smashed avocado’s future

Using lightning to make ammonia out of thin air

Machine learning potential-driven insights into pH-dependent CO₂ reduction

Physician associates provide safe care for diagnosed patients when directly supervised by a doctor

How game-play with robots can bring out their human side

Asthma: patient expectations influence the course of the disease

UNM physician tests drug that causes nerve tissue to emit light, enabling faster, safer surgery

New study identifies EMP1 as a key driver of pancreatic cancer progression and poor prognosis

XPR1 identified as a key regulator of ovarian cancer growth through autophagy and immune evasion

Flexible, eco-friendly electronic plastic for wearable tech, sensors

Can the Large Hadron Collider snap string theory?

Stuckeman professor’s new book explores ‘socially sustainable’ architecture

Synthetic DNA nanoparticles for gene therapy

New model to find treatments for an aggressive blood cancer

Special issue of Journal of Intensive Medicine analyzes non-invasive respiratory support

T cells take aim at Chikungunya virus

[Press-News.org] Why don't we all get Alzheimer's disease?