Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene variation linked to earlier onset of Alzheimer's symptoms

10.06.2008
Investigators at Washington University School of Medicine in St. Louis have identified a genetic variation associated with an earlier age of onset in Alzheimer's disease.

Unlike genetic mutations previously linked to rare, inherited forms of early-onset Alzheimer's disease — which can strike people as young as their 30s or 40s — these variants influence an earlier presentation of symptoms in people affected by the more common, late-onset form of the disease.

Two principal features characterize Alzheimer's disease in the brain: amyloid plaques and neurofibrillary tangles. The plaques contain a protein called amyloid-beta. The tangles are made of a protein called tau.

The research team analyzed DNA from 313 subjects from Washington University's Alzheimer's Disease Research Center (ADRC), focusing on locations in the tau gene that previously have been found to vary between people.

"We focused on this gene for two reasons: First, it codes for the tau protein that we find in neurofibrillary tangles, and secondly, some studies in the scientific literature show an association between the gene and Alzheimer's disease, while others do not," says principal investigator Alison M. Goate, D. Phil., the Samuel and Mae S. Ludwig Professor of Genetics in Psychiatry and professor of neurology. "Even a study from our own group had found no association between tau gene variants and Alzheimer's disease."

But this study, reported in the June 10 issue of the Proceedings of the National Academy of Sciences, changes that. One reason past studies may have produced conflicting results is that most, if not all, people have amyloid plaques in the brain years before they develop clinical symptoms of Alzheimer's.

"It's not uncommon for us to determine that an older person is fully intact mentally only to find the presence of substantial Alzheimer's pathology on examining that person's brain after death," says John C. Morris, M.D., the Harvey A. and Dorismae Friedman Distinguished Professor of Neurology and director of the ADRC and of the Harvey A. Friedman Center for Aging. "We suspect that Alzheimer lesions may be present in the brain long before we can detect any clinical symptoms."

Previous research from Goate's colleagues David M. Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology, and Anne M. Fagan, Ph.D., associate professor of neurology, measured soluble forms of amyloid-beta and tau proteins in the cerebrospinal fluid. They determined that amyloid-beta levels indicate whether or not amyloid plaques are present in the brain.

"A particular form of amyloid-beta called amyloid-beta 42, tends to be higher in the cerebrospinal fluid of normal individuals and lower in patients with Alzheimer's disease and in cognitively normal people who have amyloid plaques in the brain," says Holtzman. "Tau protein levels in the cerebrospinal fluid increase when a person starts developing dementia."

Finding those amyloid deposits once required examination of the brain after a person's death, but researchers now can detect their presence by assessing them with positron emission tomography (PET) imaging as well as measuring amyloid beta 42. When PET imaging detects amyloid in the brain, patients have lower levels of amyloid-beta 42 in their cerebrospinal fluid.

Goate's team found that four DNA sequence variants in the tau gene were associated with higher levels of tau protein in the cerebrospinal fluid. Then they divided patients into two groups. One group had evidence of plaques in the brain, while the other did not. The investigators found that the variations in the gene are only associated with an increase in tau protein levels in the cerebrospinal fluid when there is evidence of amyloid plaques in the brain.

Armed with those findings, Goate's team predicted that the variants in the tau gene that contributed to higher levels of tau protein in the cerebrospinal fluid would be associated with a younger age at the onset of Alzheimer's disease symptoms.

"So we went back to the ADRC's clinical samples, and that's exactly what we found," she says. "Individuals who carry these genetic variations that lead to higher levels of tau in cerebrospinal fluid actually have an earlier age of onset than those who carry variants that are associated with lower levels of tau."

Goate says these sequence variants in the tau gene are not linked to risk of Alzheimer's disease but rather to earlier cognitive problems once plaques have started to form in the brain. She says people who possess those genetic variants, if they are fated to develop Alzheimer's disease, will experience symptoms sooner.

"Advanced techniques in identifying markers for amyloid and tau deposition in the brains of people with Alzheimer's disease, in combination with genetic analysis, are giving us new clues about how the disease begins," says Marcelle Morrison-Bogorad, Ph.D., director of the Division of Neuroscience at the National Institute on Aging. "This study offers important information about the levels of expression of particular forms of the tau gene in the presence of brain amyloid and therefore may help us understand why the disease begins earlier in some persons than in others."

Goate says these findings lend further support to the hypothesis that amyloid-beta plaques form earlier in the cascade of Alzheimer's pathology, and that the tau protein is involved in how the disease progresses. She says more work is needed at the cellular level to figure out how the proteins interact to cause Alzheimer's symptoms, but in the meantime, she says identifying these variants in the tau gene may provide clinicians with a new target for potential therapies.

"Even when there already is evidence of amyloid deposition in the brain, if we could find a way to lower tau levels, we would predict that the onset of symptoms may be delayed," she says. "But we need to do a lot more cell biology and research in animal models before we can hope to do that."

Jim Dryden | EurekAlert!
Further information:
http://www.wustl.edu
http://www.pnas.org/cgi/doi/10/1073/pnas.0801227105

Further reports about: Alzheimer' Amyloid Amyloid-beta Genetic Plaques Tau cerebrospinal onset symptoms

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>