Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein 'fingerprint' in spinal fluid could spot Alzheimer's disease

14.12.2006
23-protein screen is highly accurate and first to be validated

Scientists collaborating at Cornell University in Ithaca and Weill Cornell Medical College in New York City have identified a panel of 23 protein biomarkers in cerebrospinal fluid that acts as a neurochemical "fingerprint," which doctors might use someday to identify patients living with Alzheimer's disease.

The research will be published in the December online-edition of the journal Annals of Neurology.

Right now, physicians rely on their clinical judgment to decide whether a particular patient has Alzheimer's rather than some other form of dementia. In many cases, the diagnosis remains uncertain until brain tissue is examined at autopsy.

"Our study is the first to use sophisticated proteomic methods to hone in on a group of cerebrospinal fluid biomarkers that are specific to autopsy-proven Alzheimer's disease. Those postmortem tests confirmed that the panel is over 90 percent sensitive in identifying people with Alzheimer's disease," says Kelvin Lee, the Samuel C. and Nancy M. Fleming Professor of Molecular and Cell Biology and associate professor of chemical and biomolecular engineering at Cornell.

Researchers at a variety of centers have long sought biomarkers in blood or cerebrospinal fluid that identify the presence of Alzheimer's pathology and distinguish it from other conditions that cause dementia.

"Some of these studies have met with limited success, but most have correlated their findings with patient's clinical symptoms rather than working with the gold-standard of autopsy-proven Alzheimer's," notes Norman Relkin, M.D., associate professor of clinical neurology and neuroscience at Weill Cornell and director of the Memory Disorders Program at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Erin Finehout, Ph.D. ‘05, the lead author on the research who had been a doctoral student in Lee's laboratory, said this has great potential to impact human health. "Typically, Alzheimer's disease is not diagnosed until the disease has already caused some amount of dementia," she said. "Having a chemical test available may allow patients to be diagnosed earlier in the course of the disease."

The Cornell study combined cutting edge "proteomics" technology, detailed image analysis, and complex computational and statistical analyses to simultaneously compare 2,000 cerebrospinal fluid proteins from 34 patients with autopsy-proven Alzheimer's disease to those of 34 age-matched controls without the disease.

"Just as the human genome reflects the array of genes a person possesses, the ‘proteome' is the vast collection of proteins expressed by those genes," said Lee. "Essentially we used high-tech methods to contrast the proteomes of Alzheimer's patients against those of a control cohort that included people with other forms of dementia as well as healthy individuals, looking for key differences between the two groups."

This effort yielded intriguing results: 23 proteins that individually might not point to Alzheimer's but together formed an identifying pattern or "fingerprint" specific to the illness.

"Although it need not have turned out that way, several of the 23 markers that emerged from this analysis proved to be proteins with known links to the pathological mechanisms of Alzheimer's disease," said Relkin.

For example, some of the biomarkers are associated with proteins that clog the brains of Alzheimer's patients. Others molecules were linked to inflammation, also a part of Alzheimer's brain pathology. Still other proteins in the panel were linked to synaptic dysfunction – the breakdown of communication between brain cells that occurs as Alzheimer's disease progresses.

"A subsequent validation group of 10 patients with suspected Alzheimer's and 18 healthy and demented control subjects turned up similar results," said Relkin. "Based on their clinical symptoms, we found the new screen to have 93 percent sensitivity to probable cases of Alzheimer's and a 90 percent accuracy in avoiding false diagnoses."

Despite their excitement over the new findings, the researchers stress that the results still need to be replicated in much larger populations.

"There's a federally funded, multicenter trial going on right now that involves many more patients, in which many enrollees will undergo spinal taps and brain imaging," Relkin said. "We hope to link into that effort to expand on these findings."

The dream of a highly accurate Alzheimer's disease test that patients and doctors could use to diagnose illness and guide treatment is the ultimate goal. But the finding has important implications for current Alzheimer's research, as well.

"You might have a promising treatment for the disease, but how can you know for sure that it's impacting on the underlying pathology, rather than just easing outward symptoms as most of the drugs that we have now do"" Relkin said.

"We are hopeful that by monitoring changes in these cerebrospinal biomarkers, we can actually track the effectiveness – or lack thereof – of experimental drugs."

He continued: "In fact, we are now using this panel to study the effects of a promising new experimental treatment for Alzheimer's called IVIg (intravenous immunoglobulin). "Data gleaned from the use of this 23-protein screen suggests that IVIg may be having a positive impact on underlying disease processes."

And while a standard test for spotting early Alzheimer's disease is not in doctors' offices today, it could be in the not-too-distant future.

"These findings speak to the practicality of using biological markers for discerning whether symptoms are reflective of Alzheimer's, another dementia or normal aging," Relkin said. "And in this study, we're offering a much more sophisticated and better-validated approach than has ever been presented before."

Blaine Friedlander | EurekAlert!
Further information:
http://www.cornell.edu

Further reports about: Alzheimer' Relkin cerebrospinal cerebrospinal fluid dementia

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

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

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>