Featured Research

from universities, journals, and other organizations

Genetic markers ID second Alzheimer's pathway

Date:
April 4, 2013
Source:
Washington University School of Medicine
Summary:
Researchers have identified a new set of genetic markers for Alzheimer's disease that point to a second pathway through which the disease develops.

Both a tangle (top left) and a plaque (bottom right) can be seen in the brain of a patient with Alzheimer’s disease.
Credit: Nigel Cairns, PhD

Researchers at Washington University School of Medicine in St. Louis have identified a new set of genetic markers for Alzheimer's that point to a second pathway through which the disease develops.

Related Articles


Much of the genetic research on Alzheimer's centers on amyloid-beta, a key component of brain plaques that build up in the brains of people with the disease.

In the new study, the scientists identified several genes linked to the tau protein, which is found in the tangles that develop in the brain as Alzheimer's progresses and patients develop dementia. The findings may help provide targets for a different class of drugs that could be used for treatment.

The researchers report their findings online April 24 in the journal Neuron.

"We measured the tau protein in the cerebrospinal fluid and identified several genes that are related to high levels of tau and also affect risk for Alzheimer's disease," says senior investigator Alison M. Goate, DPhil, the Samuel and Mae S. Ludwig Professor of Genetics in Psychiatry. "As far as we're aware, three of these genes have no effect on amyloid-beta, suggesting that they are operating through a completely different pathway."

A fourth gene in the mix, APOE, had been identified long ago as a risk factor for Alzheimer's. It has been linked to amyloid-beta, but in the new study, APOE appears to be connected to elevated levels of tau. Finding that APOE is influencing more than one pathway could help explain why the gene has such a big effect on Alzheimer's disease risk, the researchers say.

"It appears APOE influences risk in more than one way," says Goate, also a professor of genetics and co-director of the Hope Center for Neurological Disorders. "Some of the effects are mediated through amyloid-beta and others by tau. That suggests there are at least two ways in which the gene can influence our risk for Alzheimer's disease."

The new research by Goate and her colleagues is the largest genome-wide association study (GWAS) yet on tau in cerebrospinal fluid. The scientists analyzed points along the genomes of 1,269 individuals who had undergone spinal taps as part of ongoing Alzheimer's research.

Whereas amyloid is known to collect in the brain and affect brain cells from the outside, the tau protein usually is stored inside cells. So tau usually moves into the spinal fluid when cells are damaged or die. Elevated tau has been linked to several forms of non-Alzheimer's dementia, and first author Carlos Cruchaga, PhD, says that although amyloid plaques are a key feature of Alzheimer's disease, it's possible that excess tau has more to do with the dementia than plaques.

"We know there are some individuals with high levels of amyloid-beta who don't develop Alzheimer's disease," says Cruchaga, an assistant professor of psychiatry. "We don't know why that is, but perhaps it could be related to the fact that they don't have elevated tau levels."

In addition to APOE, the researchers found that a gene called GLIS3, and the genes TREM2 and TREML2 also affect both tau levels and Alzheimer's risk.

Goate says she suspects changes in tau may be good predictors of advancing disease. As tau levels rise, she says people may be more likely to develop dementia. If drugs could be developed to target tau, they may prevent much of the neurodegeneration that characterizes Alzheimer's disease and, in that way, help prevent or delay dementia.

The new research also suggests it may one day be possible to reduce Alzheimer's risk by targeting both pathways.

"Since two mechanisms apparently exist, identifying potential drug targets along these pathways could be very useful," she says. "If drugs that influence tau could be added to those that affect amyloid, we could potentially reduce risk through two different pathways."


Story Source:

The above story is based on materials provided by Washington University School of Medicine. The original article was written by Jim Dryden. Note: Materials may be edited for content and length.


Journal Reference:

  1. Carlos Cruchaga, JohnS.K. Kauwe, Oscar Harari, ShengChih Jin, Yefei Cai, CelesteM. Karch, BrunoA. Benitez, AmandaT. Jeng, Tara Skorupa, David Carrell, Sarah Bertelsen, Matthew Bailey, David McKean, JoshuaM. Shulman, PhilipL. DeJager, Lori Chibnik, DavidA. Bennett, SteveE. Arnold, Denise Harold, Rebecca Sims, Amy Gerrish, Julie Williams, ViviannaM. VanDeerlin, VirginiaM.-Y. Lee, LeslieM. Shaw, JohnQ. Trojanowski, JonathanL. Haines, Richard Mayeux, MargaretA. Pericak-Vance, LindsayA. Farrer, GerardD. Schellenberg, ElaineR. Peskind, Douglas Galasko, AnneM. Fagan, DavidM. Holtzman, JohnC. Morris, AlisonM. Goate. GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease. Neuron, 2013; DOI: 10.1016/j.neuron.2013.02.026

Cite This Page:

Washington University School of Medicine. "Genetic markers ID second Alzheimer's pathway." ScienceDaily. ScienceDaily, 4 April 2013. <www.sciencedaily.com/releases/2013/04/130404122102.htm>.
Washington University School of Medicine. (2013, April 4). Genetic markers ID second Alzheimer's pathway. ScienceDaily. Retrieved January 31, 2015 from www.sciencedaily.com/releases/2013/04/130404122102.htm
Washington University School of Medicine. "Genetic markers ID second Alzheimer's pathway." ScienceDaily. www.sciencedaily.com/releases/2013/04/130404122102.htm (accessed January 31, 2015).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, January 31, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

NFL Concussions Down; Still on Parents' Minds

NFL Concussions Down; Still on Parents' Minds

AP (Jan. 30, 2015) The NFL announced this week that the number of game concussions dropped by a quarter over last season. Still, the dangers of the sport still weigh on players, and parents&apos; minds. (Jan. 30) Video provided by AP
Powered by NewsLook.com
Study Shows Newborn Chicks Count From Left to Right Just Like Humans

Study Shows Newborn Chicks Count From Left to Right Just Like Humans

Buzz60 (Jan. 30, 2015) Researchers for the first time identified human&apos;s innate preference for associating low and high numbers with the left and right respectively in another species. Jen Markham (@jenmarkham) explains. Video provided by Buzz60
Powered by NewsLook.com
Best Mood Elevating, Feel Good Shakes & Smoothies

Best Mood Elevating, Feel Good Shakes & Smoothies

Buzz60 (Jan. 30, 2015) You can elevate your mood by having a meal in a glass. Fitness and nutrition expert John Basedow (@JohnBasedow) offers the best &apos;feel good&apos; smoothies and shakes chock full of depression-relieving ingredients...including apples, berries, lemons, cucumbers, papaya, kiwi, spinach, kale, whey protein, matcha, ginger, turmeric and cinnamon. Video provided by Buzz60
Powered by NewsLook.com
Poll Says Firstborn Is Responsible, Youngest Is Funnier

Poll Says Firstborn Is Responsible, Youngest Is Funnier

Newsy (Jan. 30, 2015) According to a poll out of the U.K., eldest siblings feel more responsible and successful than their younger siblings. 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