A new set of genetic markers for Alzheimer’s disease that point to a second pathway through which the disease can develop have been identified by researchers at Washington University School of Medicine.
The researchers hope these new genetic markers will help provide targets for a different class of drugs that could be used to treat the disease.
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In the new study, researchers identified several genes linked to the tau protein, which is found in the tangles that develop in the brain as Alzheimer’s progresses.
Researchers measured the tau protein in the cerebrospinal fluid and identified several genes related to high levels of the protein and that also affect risk for Alzheimer’s disease.
Most of the genetic research on Alzheimer’s currently centres on amyloid-beta, a key component of brain plaques that build up in the brains of people with the disease.
However, senior investigator Alison M Goate said that, as far as her and her team were aware, three of the genes they identified have no effect on amyloid-beta, suggesting they are operating through a completely different pathway.
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By GlobalDataThe researchers suspect that changes in tau could be a strong indicator of advancing Alzheimer’s.
"We know there are some individuals with high levels of amyloid-beta who don’t develop Alzheimer’s disease," said Carlos Cruchaga, an assistant professor of psychiatry at the university.
"We don’t know why that is, but perhaps it could be related to the fact that they don’t have elevated tau levels."
Researchers also found that a gene, APOE, which is a known indicator for Alzheimer’s because of its link to amyloid-beta, is also connected to elevated levels of tau.
Researchers believe that if they can establish that this gene affects more than one pathway it would explain why it has such a big effect on Alzheimer’s disease risk.
"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.
The scientists say their research could lead to drugs being developed to specifically target the tau protein to prevent much of the neurodegeneration that characterises Alzheimer’s disease and help prevent dementia.
It also suggests that in the future it may be possible to reduce Alzheimer’s risk by targeting both pathways.
The study is the largest genome-wide association study (GWAS) yet on tau in cerebrospinal fluid.
It involved analysing the genomes of 1,269 individuals who had undergone spinal taps as part of ongoing Alzheimer’s research.
The scientists’ full research will published in Neuron journal later in the month.
Image: The study is the largest genome-wide association study (GWAS) yet on tau in cerebrospinal fluid, which involved 1,269 individuals. Photo: Courtesy of Nigel Cairns, PhD, Washington University School of Medicine.
