Aggressive Alzheimer's Disease Gene Discovered, May Help Find Treatments
Scientists may be able to uncover the speed that Alzheimer’s disease progresses using a genetic test, researchers say.
Patients with a gene variation linked to higher levels of a protein associated with the disease get sicker two to seven times as fast as others, according to a study published today in PLoS Genetics.
The finding may be a boon to drugmakers looking to test Alzheimer’s treatments by pinpointing which patients would develop symptoms more quickly, said Alison Goate, a professor of genetics at the Washington University in St. Louis who was an author of the study. Pfizer Inc., Johnson & Johnson and Eli Lilly & Co. are testing medicines aimed at treating the disease.
“Clinical trials are immensely expensive and we want to see a meaningful change in a short period of time,” Goate said in a telephone interview. “If individuals are progressing at different speeds, that’s hard to do, but if you pick individuals who are more likely to progress more rapidly, you may see a meaningful change in a shorter period.”
Alzheimer’s and other dementias will afflict 35.6 million people this year, according to a report from Alzheimer’s Disease International, a London-based federation. The ailment destroys brain cells progressively, making it difficult for patients to think, remember, and function.
The time it takes patients to decline because of Alzheimer’s varies, from five or six years to more than two decades, Goate said.
The gene variation doesn’t predict who will get the condition, said Carlos Cruchaga, a researcher in psychiatry at the Washington University School of Medicine and an author of the study.
The gene, known as rs1868402, normally removes phosphate from tau, a protein that helps supply nutrients to cells in the brain and has been shown to be involved in Alzheimer’s. An abnormal form of the gene may leave phosphate in tau, causing the protein to become tangled and stop working, Goate said.
“This work suggests that if you could modify tau levels in mildly demented individuals, you could slow the progression of disease,” said Goate. That could mean patients stay independent longer, she said.
The association was made by examining the genes of hundreds of patients from multiple studies to see if there were any genetic segments in common related to the tau protein found in the Alzheimer’s patients. Once the abnormal gene was located, researchers examined samples of cerebral-spinal fluid and confirmed the patients also had bad tau.
To examine the progression, the researchers used 109 patients from one study and 150 patients from another.
Previous genetic discoveries in Alzheimer’s research have been linked to a different protein, amyloid. Amyloid is the target of the experimental drugs being tested by New York-based Pfizer, Johnson & Johnson of New Brunswick, New Jersey, and Indianapolis-based Lilly.
“This indicates that tau may be a better marker for rate and progression of the disease than amyloid,” said Bill Thies, chief medical and scientific officer for the Chicago-based Alzheimer’s Association. In July, the group said guidelines that have been in use in the U.S. for 25 years need to change so doctors can make earlier and more-accurate diagnoses.
TauRX Pharmaceuticals Ltd., a closely held Singaporean drugmaker, is working on an Alzheimer’s treatment based on tau, and is collaborating with German drugmaker Bayer AG to make an imaging test for the protein.
The study was partly funded by a grant from London-based drugmaker AstraZeneca Plc.
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