Genetic markers for Alzheimer's identified

Scientists have identified a new set of genetic markers for Alzheimer's which may help predict the risk of developing the neurodegenerative disease.
Researchers at Washington University School of Medicine in St Louis identified genetic markers that point to a second pathway through which Alzheimer's develops.
They 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.
"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," said senior investigator Alison M Goate, 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," Goate said.
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 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," said Goate, also a professor of genetics and co-director of the Hope Center for Neurological Disorders.

Scientists analysed 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 said 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. We don't know why that is, but perhaps it could be related to the fact that they don't have elevated tau levels," Cruchaga said in the journal Neuron.
Goate said she suspected changes in tau may be good predictors of advancing disease. As tau levels rise, she said people may be more likely to develop dementia.
If drugs could be developed to target tau, they may prevent much of the neurodegeneration that characterises Alzheimer's disease and, in that way, help prevent or delay dementia.