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 Hopkins researchers ID neurotransmitter that helps cancers progress
25.04.2019 | Johns Hopkins Medicine

nachricht Trigger region found for absence epileptic seizures
25.04.2019 | RIKEN

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Full speed ahead for SmartEEs at Automotive Interiors Expo 2019

Flexible, organic and printed electronics conquer everyday life. The forecasts for growth promise increasing markets and opportunities for the industry. In Europe, top institutions and companies are engaged in research and further development of these technologies for tomorrow's markets and applications. However, access by SMEs is difficult. The European project SmartEEs - Smart Emerging Electronics Servicing works on the establishment of a European innovation network, which supports both the access to competences as well as the support of the enterprises with the assumption of innovations and the progress up to the commercialization.

It surrounds us and almost unconsciously accompanies us through everyday life - printed electronics. It starts with smart labels or RFID tags in clothing, we...

Im Focus: Energy-saving new LED phosphor

The human eye is particularly sensitive to green, but less sensitive to blue and red. Chemists led by Hubert Huppertz at the University of Innsbruck have now developed a new red phosphor whose light is well perceived by the eye. This increases the light yield of white LEDs by around one sixth, which can significantly improve the energy efficiency of lighting systems.

Light emitting diodes or LEDs are only able to produce light of a certain colour. However, white light can be created using different colour mixing processes.

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

High-efficiency thermoelectric materials: New insights into tin selenide

25.04.2019 | Materials Sciences

Salish seafloor mapping identifies earthquake and tsunami risks

25.04.2019 | Earth Sciences

Using DNA templates to harness the sun's energy

25.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>