Featured Research

from universities, journals, and other organizations

Researchers Develop Blood Test To Diagnose Alzheimer's-Type Changes In Mice

Date:
March 22, 2002
Source:
Washington University School Of Medicine
Summary:
Researchers have for the first time used a blood test to identify Alzheimer’s-type changes in living mice. The test, developed by researchers at Washington University School of Medicine in St. Louis and Eli Lilly and Company, predicts the amount of amyloid plaque in an animal’s brain, a hallmark of Alzheimer’s disease. To date, the only way to definitively diagnose this disease in humans is by examining a person’s brain after death.

St. Louis, March 22, 2002 — Researchers have for the first time used a blood test to identify Alzheimer’s-type changes in living mice. The test, developed by researchers at Washington University School of Medicine in St. Louis and Eli Lilly and Company, predicts the amount of amyloid plaque in an animal’s brain, a hallmark of Alzheimer’s disease. To date, the only way to definitively diagnose this disease in humans is by examining a person’s brain after death.

Related Articles


“We don’t know if this finding in mice will apply to humans,” says David M. Holtzman, M.D., the Charlotte and Paul Hagemann Associate Professor of Neurology and associate professor of molecular biology and pharmacology at the School of Medicine. “If it does, it has the potential to provide a non-invasive means of detecting Alzheimer’s pathology even before clinical symptoms appear.”

Holtzman led the Washington University research team and Steven M. Paul, M.D., group vice president at Lilly Research Laboratories, led the Lilly team. Washington University research fellow Ronald B. DeMattos, Ph.D., was first author; Lilly’s Kelly R. Bales, was a co-first author. The study is published in the March 22 issue of Science.

Recent studies have revealed physical changes that can begin in the brains of Alzheimer’s patients 10 to 20 years before symptoms arise. For reasons not entirely understood, potentially dangerous amounts of a protein called amyloid-b (Ab) begin to build up in these individuals. If enough Ab clumps together in the brain, it forms amyloid plaques, a key feature of Alzheimer’s disease.

“Brain plaques are somewhat analogous to the plaques characteristic of arteriosclerosis,” explains Paul. “If you have a heart attack at age 65, the atherosclerotic process that caused that event probably started decades beforehand. Since we now know that Alzheimer’s pathology starts well before symptoms appear, we’re hoping it may be possible to develop a test that predicts the presence of amyloid plaques and, ultimately, the risk of dementia, similar to performing an angiogram to predict an impending heart attack.”

The team examined 49 mice with a mutation in the gene for amyloid precursor protein (APP) similar to the genetic abnormality found in some families with a strong history of Alzheimer’s disease. All the mice developed plaques within a year, though to varying degrees. The researchers took advantage of these differences to investigate potential factors that predict the extent of plaque formation.

First, they measured baseline levels of two types of Ab in the animals’ blood, Ab40 and Ab42. The mice then were injected with m266 – an antibody that the team previously discovered draws Ab out of the brain and into the surrounding blood without harming the animals – and were periodically retested for blood Ab. After 24 hours, the researchers examined each animal’s brain tissue for plaques, focusing on two key regions involved in Alzheimer’s disease: the hippocampus and the cingulate cortex.

Before m266 injection, the amount of Ab in the animals’ blood did not correlate to the number of plaques in their brains. But within five minutes of m266 injection, Ab levels increased dramatically and did correlate with the amount of brain amyloid. This suggests that blood Ab levels do not reflect the progression of the disease unless the animal has been given m266.

According to DeMattos, blood Ab levels in humans also do not reflect the amount of amyloid plaques in the brain. “The truly novel finding of our experiment is that a simple injection of m266 altered the metabolism of Ab and unmasked important correlations with brain pathology. Hopefully, we also will be able to alter the metabolism of Ab in humans.”

The team used their data to develop potential models for estimating amyloid levels in the brain. Several factors, including overall levels of Ab after m266 injection and Ab40 levels 24 hours after injection, accurately revealed the extent of amyloid deposition in the brains of these mice. Using these factors, the team developed a rough diagnostic procedure to determine “high” or “low” plaque burden in the animals.

“This has obvious implications for developing a similar blood test for brain amyloid load in humans,” says Holtzman. “Though we will not be able to detect risk in someone who has not begun to accumulate amyloid, we hope to predict the disease well before symptoms appear. Such a test also could distinguish individuals suffering from dementia caused by Alzheimer’s from those with other types of dementia, and may help us evaluate an individual’s response to particular medical therapies.”

###

Reference:

DeMattos RB, Bales KR, Cummins DJ, Paul SM, Holtzman DM. Brain to plasma amyloid-b efflux: A measure of brain amyloid burden in a mouse model of Alzheimer’s disease. Science, 295, 2264-2267, March 22, 2002.

Funding from Eli Lilly and Co. and the National Institute on Aging supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Researchers Develop Blood Test To Diagnose Alzheimer's-Type Changes In Mice." ScienceDaily. ScienceDaily, 22 March 2002. <www.sciencedaily.com/releases/2002/03/020322075230.htm>.
Washington University School Of Medicine. (2002, March 22). Researchers Develop Blood Test To Diagnose Alzheimer's-Type Changes In Mice. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2002/03/020322075230.htm
Washington University School Of Medicine. "Researchers Develop Blood Test To Diagnose Alzheimer's-Type Changes In Mice." ScienceDaily. www.sciencedaily.com/releases/2002/03/020322075230.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
Yoga Could Be As Beneficial For The Heart As Walking, Biking

Yoga Could Be As Beneficial For The Heart As Walking, Biking

Newsy (Dec. 17, 2014) Yoga can help your weight, blood pressure, cholesterol and heart just as much as biking and walking does, a new study suggests. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins