A massive scientific effort has found five new gene variants linked to Alzheimer’s disease.

The undertaking involved analyzing the genomes of nearly 40,000 people with and without Alzheimer’s. The mammoth task was undertaken by two separate research consortiums in the U.S. and in Europe, which collaborated to confirm each other’s results.

The finding may lead to earlier detection of Alzheimer’s disease as well as to new treatments, says William Theis, PhD, chief scientific officer for the Alzheimer’s Association.

“We will see more and more of these kinds of genes. And the more we have, the more we will be able to define a person’s risk of Alzheimer’s disease and the more possibilities we will have for therapeutic interventions,” Theis tells WebMD.

Before the new discovery, four genes had been definitively linked to Alzheimer’s. Three of them affect only the risk of relatively rare forms of Alzheimer’s. The fourth is APOE, until now the only gene known to affect risk of the common, late-onset form of Alzheimer’s.

All five of the newly discovered genes affect this more common form of the disease. None is as powerful as APOE. Roughly 27% of Alzheimer’s disease can be attributed to the five new gene variants, calculates Julie Williams, PhD, of the U.K.’s Cardiff University. Some 60% of Alzheimer’s disease can be attributed to the five new genes plus APOE, she says.

“But you will never have the perfect treatments to take out all the disease-causing effects of these genes,” Williams tells WebMD. “The point is that now there is the possibility to take out a considerable amount of disease if we take these results forward, understand the Alzheimer’s disease process, and make interventions, including lifestyle changes.”

Williams led a consortium of European researchers that identified two of the new Alzheimer’s genes. Her group also confirmed that three gene variants identified by a U.S. research consortium were indeed linked to Alzheimer’s.

Theis notes that Alzheimer’s is a very complex disease, and that eventually as many as 100 genes may be involved. Even so, the new findings represent a large chunk of Alzheimer’s risk.

“If you look at all the Alzheimer’s genes we now know, we have accounted for 20% of the causal risk of Alzheimer’s disease and 32% of the genetic risk,” Williams tells WebMD.

One of the leaders of the U.S. consortium is Margaret A. Pericak-Vance, PhD, director of the Institute for Human Genomics at the University of Miami Miller School of Medicine.

“This is an unprecedented story of collaboration. The world is coming together to say, ‘We are going to beat this thing,'” Pericak-Vance tells WebMD. “These are not ‘possible’ Alzheimer genes; they are definite and further confirmed by the European studies. These are robust findings we can take to the next level.”

Perhaps the greatest value of the gene studies is the clues they offer to the causes of Alzheimer’s. The new genes affect three important pathways:

• Endocytosis, the process by which large molecules — such as the amyloid precursor protein — get into brain cells.
• Inflammatory immune responses, which seem to go awry in Alzheimer’s disease.
• Lipid processing. The brain makes its own cholesterol. APOE — and now a new gene called ABCA7 — are involved in this process. Misprocessing of cholesterol could contribute to Alzheimer’s, Williams speculates.

“Each one of these metabolic pathways becomes a place to look at interventions that may lower the risk of Alzheimer’s disease or may even result in a treatment,” Theis says.

Both the U.S. and European research teams report their findings in the April 3 advance online issue of Nature Genetics.

source: webMD