(Press-News.org) With a lack of effective treatments for Alzheimer's, most of us would think long and hard about whether we wanted to know years in advance if we were genetically predisposed to develop the disease. For researchers, however, such knowledge is a window into Alzheimer's disease's evolution.
Understanding the biological changes that occur during the clinically "silent" stage — the years before symptoms appear — provides clues about the causes of the disease and may offer potential targets for drugs that will stop it from progressing.
In a new study, researchers at UCLA have identified chemical changes taking place in the brains of people destined to develop familial Alzheimer's disease at least 10 years before symptoms or diagnoses occur. Reporting in the current online edition of the journal Archives of Neurology, John Ringman, a UCLA associate professor of neurology, and colleagues identified changes in 56 proteins, including increases in the amyloid protein long associated with Alzheimer's, inflammatory markers and other proteins related to the brain's synapses, the connections between neurons through which these brain cells communicate with each other.
Familial Alzheimer's and sporadic, late-onset Alzheimer's are distinct forms of what many consider a single disease. The majority of Alzheimer's cases are sporadic and late-onset, developing after age 65; the causes of this disease type are not completely understood but are at least partly genetic. Familial Alzheimer's (FAD), a rare form of the disease caused by certain gene mutations, affects less than 2 percent of patients. It is typically early-onset, developing before age 65, and it is inherited — all offspring in the same generation have a 50 chance of developing FAD if one of their parents had it.
For this study, researchers developed protein profiles drawn from the cerebrospinal fluid of 14 FAD mutation carriers and compared them with five related non-carriers. In all, they identified 56 proteins that showed significant differences between carriers and non-carriers. Fourteen of these proteins had been reported in prior studies on late-onset Alzheimer's (including APP, transferrin and other inflammatory markers), but many others were unique to this study, including calsyntenin 3, AMPA 4 glutamate receptor and osteopontin. Normally, these proteins are thought to play a role in the growth and remodeling of synapses, and their alteration in pre-symptomatic Alzheimer's may represent an early manifestation of the loss of these critical structures.
"Unfortunately, we do not yet have effective medications to stop the progression of Alzheimer's," said Ringman, who works at UCLA's Mary S. Easton Center for Alzheimer's Disease Research. "In this study, we've identified chemical changes occurring in the brains of persons destined to develop Alzheimer's disease 10 years or more prior to the expression of symptoms. By studying the cerebrospinal fluid of persons developing Alzheimer's disease at a relatively young age with cutting-edge protein chemical techniques, we found changes in markers reflecting inflammation as well as the breakdown of synapses.
"This provides potential new targets for drug interventions, and it helps elucidate the degree to which FAD and late-onset Alzheimer's are similar and to what degree they are distinct. Such knowledge may ultimately allow us to tailor our treatments to individuals, depending on the 'type' of Alzheimer's they have."
The study, funded in part by the pharmaceutical company Pfizer Inc., a grant from the state of California and other sources, was performed at UCLA's Easton Center, one of 10 centers currently receiving funding from the state. State funding helps these centers provide specialized care for patients with Alzheimer's disease and other forms of dementia and their families, and it enables the centers to provide training for those engaged in the diagnosis and care of patients with dementia in California.
INFORMATION:
Additional study authors included Gregory Cole, Sophie Sokolow, Karen Gylys, Daniel H. Geschwind, Jeffrey L. Cummings and Hong I. Wan from UCLA; Howard Schulman, Chris Becker and Ted Jones from Caprion Proteomics U.S.; and Yuchen Bai and Fred Immermann from Pfizer Inc.
The Mary S. Easton Center for Alzheimer's Disease Research at UCLA is part of the UCLA Department of Neurology, which encompasses more than 20 disease-related research programs, along with large clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranked first among its peers nationwide in National Institutes of Health funding (2002).
For more news, visit the UCLA Newsroom and follow us on Twitter.
END
University of California, Davis, researchers have proposed a radical new way of thinking about the chemical reactions between water and metal oxides, the most common minerals on Earth. Their work appears in the current issue of the journal Nature Materials.
The new paradigm could lead to a better understanding of corrosion and how toxic minerals leach from rocks and soil. It could also help in the development of "green" technology: new types of batteries, for example, or catalysts for splitting water to produce hydrogen fuel.
"This is a global change in how people should ...
CHAMPAIGN, Ill. — A turning point in the history of life occurred 2 to 3 billion years ago with the unprecedented appearance and dramatic rise of molecular oxygen. Now researchers report they have identified an enzyme that was the first – or among the first – to generate molecular oxygen on Earth.
The new findings, reported in the journal Structure, build on more than a dozen previous studies that aim to track the molecular evolution of life by looking for evidence of that history in present-day protein structures. These studies, led by University of Illinois crop sciences ...
SAN DIEGO — The investigational drug ganetespib, a synthetic second-generation Hsp90 inhibitor, slowed the growth of cancer cells taken from non-small cell lung cancer tumors with a mutation in the KRAS gene. The drug was even more active when combined with traditional lung cancer treatments and other investigational targeted therapies, according to preclinical study data.
David A. Proia, Ph.D., and Jaime Acquaviva, Ph.D., scientists at Synta Pharmaceuticals Corp., presented the data at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy ...
SAN DIEGO -- Smoking may be associated with the development of molecular features of cancer in the large airway epithelium. In the small airway epithelium, molecular cancerization is associated with development of chronic obstructive pulmonary disease, according to recent data.
"We are striving to find the earliest molecular changes that are induced by environmental stressors — in this case, smoking," said Renat Shaykhiev, M.D., Ph.D., assistant professor of genetic medicine at Weill Cornell Medical College, who presented the findings at the AACR-IASLC Joint Conference ...
Preventing mother to child transmission of HIV in Zimbabwe
In this week's PLoS Medicine, Andrea Ciaranello of Massachusetts General Hospital, Boston, USA and colleagues find, using a simulation model, that implementation of the latest WHO PMTCT (prevention of mother to child transmission of HIV) guidelines must take place in conjunction with improving access to PMTCT programs, increasing retention of women in care, and supporting adherence to drugs, in order to eliminate pediatric HIV in Zimbabwe.
The authors say: "Although PMTCT uptake in low- and middle-income countries ...
Limited use of compulsory licensing of pharmaceuticals to protect public health
Reed Beall and Randall Kuhn of the University of Denver, USA describe in this week's PLoS Medicine their findings from an analysis of use of compulsory licenses for pharmaceutical products by World Trade Organization members since 1995. Specifically, the authors investigated the impact of the 2001 Doha Declaration on trends in compulsory licensing of pharmaceuticals. They highlight the need for further systematic evaluation of global health agreements.
###Funding: No direct funding was received ...
Long-term consequences of venous thrombosis
Linda Flinterman of Leiden University, the Netherlands and colleagues report in this week's PLoS Medicine on the long-term mortality rate for individuals who have experienced a first venous thrombosis or pulmonary embolism. They describe an ongoing elevated risk of death for individuals who had experienced a venous thrombosis or pulmonary embolism as compared to controls, for up to eight years after the event.
The authors say: "To our knowledge, this has been the first study to calculate mortality rates compared with the general ...
Jason Nickerson and Amir Attaran of the University of Ottawa, Canada examine in this week's PLoS Medicine the vast inequities in medical pain relief around the world, arguing that the imbalance has arisen from restrictive drug laws designed to prevent access to illegal substances, and proposing that the global control of licit narcotics be shifted from the International Narcotic Control Board to WHO.
The authors say: "Transferring the public health responsibility for controlled medicines from INCB to WHO would end the impossibly contradictory situation in which INCB ...
GAINESVILLE, Fla. --- Celebrities are channeling a distant relative with what Harper's Bazaar describes as the latest trend in nail fashion for 2012: claws. But this may not be the first time primates traded their nails for claws.
A new study co-authored by a University of Florida researcher examines the first extinct North American primate with a toe bone showing features associated with the presence of both nails and a grooming claw, indicating our primate ancestors may have traded their flat nails for raised claws for functional purposes, much like pop icons Adele ...
BIRMINGHAM, Ala. – Using marijuana carries legal risks, but a new study shows that the consequences of occasionally lighting up do not include long-term loss of lung function, according to a new study by University of Alabama at Birmingham researchers published in the January 11, 2012, issue of the Journal of the American Medical Association.
Marijuana is the most commonly used illicit drug in the United States, according to the National Survey on Drug Use and Health. In 2009, 16.7 million Americans ages 12 and older reported using marijuana at least once in the month ...
