A second pathway through which Alzheimer’s develops has been discovered after researchers identified a new set of genetic markers for the disease.
Most Alzheimer’s genetic research focuses on amyloid-beta, which contributes to the formation of plaques found in the brains of people suffering from Alzheimer’s.
In this study, published in the journal Neuron, researchers were able to identify genes linked to the tau protein, a protein which develops in the brain as Alzheimer’s slowly progresses.
The findings may help provide targets for a different class of drugs that could be used for treatment.
According to the senior investigator of the study, Alison M. Goate, DPhil, the Samuel and Mae S. Ludwig Professor of Genetics in Psychiatry:
”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. 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.”
However, they also noted that a fourth gene, called APOE, was linked to elevated levels of the tau protein. Previous studies have found an association with the gene and amyloid-beta, which indicates that this gene influences more than one pathway.
Goate, professor of genetics and co-director of the Hope Center for Neurological Disorders, said:
“It appears APOE influences risk in more than one way. 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.”
In the largest study on tau in cerebrospinal fluid, the researchers analyzed points along the genome in a total of 1,269 people who underwent spinal taps as part of a research project.
The tau protein is stored inside brain cells, in contrast to amyloid, which is known to affect brain cells from the outside.
Elevated levels of tau have been linked to several different forms of dementia not associated with Alzheimer’s.
The researchers believe that excess tau may has more to do with dementia in Alzheimer’s patients than plaques.
Cruchaga, an assistant professor of psychiatry, said: “We know there are some individuals with high levels of amyloid-beta who don’t develop Alzheimer’s disease. We don’t know why that is, but perhaps it could be related to the fact that they don’t have elevated tau levels.”
The genes that were found to affect tau levels and Alzheimer’s risk were: GLIS3, TREM2, APOE, and TREML2.
Goate believes that tau levels could be a good indicator of Alzheimer’s risk and the development of the disease.
In addition, she hopes that if new drugs could target tau they could effectively prevent neurodegeneration which causes dementia.
Goate concluded: “Since two mechanisms apparently exist, identifying potential drug targets along these pathways could be very useful. If drugs that influence tau could be added to those that affect amyloid, we could potentially reduce risk through two different pathways.”
A previous study published in the journal Diabetes identified a relationship between obesity and disorders linked to the tau protein. This indicates that the protein may be associated with a wide range of disorders.
Written by Joseph Nordqvist