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Gene mutation in immune system is linked to Alzheimer's disease

  • Article by: GINA KOLATA
  • New York Times
  • November 14, 2012 - 7:35 PM

Researchers have for years concentrated on one hallmark of Alzheimer's disease: the production of toxic shards of a protein that accumulate in plaques on the brain.

But now, in a surprising coincidence, two groups of researchers working from different starting points have converged on a mutated gene involved in another aspect of Alzheimer's disease: the immune system's role in protecting against the disease. The mutation is suspected of interfering with the brain's ability to prevent the buildup of plaque.

The discovery, researchers said, provides clues to how and why the disease progresses. The gene, known as TREM2, is only the second found to increase Alzheimer's risk substantially in older people.

"It points very specifically to a potential metabolic pathway that you could intervene in to change the course of Alzheimer's disease," said William Thies, chief medical and scientific officer of the Alzheimer's Association.

Much work remains to be done before scientists understand precisely how the gene mutation leads to Alzheimer's, but already there are some indications from studies in mice. When the gene is not mutated, white blood cells in the brain spring into action, gobbling up and eliminating the plaque-forming toxic protein, beta amyloid. As a result, Alzheimer's can be staved off or averted.

But when the gene is mutated, the brain's white blood cells are hobbled, making them less effective in their attack on beta amyloid.

People with the mutated gene have a threefold to fivefold increase in the likelihood of developing Alzheimer's disease in old age.

The intact gene, said John Hardy of University College London, "is a safety net." And those with the mutation, he added, "are living life without a safety net." Hardy is lead author of one of the papers.

The discovery also suggests that a new type of drug could be developed to enhance the gene's activity, perhaps allowing the brain's white blood cells to do their work.

"The field is in desperate need of new therapeutic agents," said Alison Goate, an Alzheimer's researcher at Washington University in St. Louis who contributed data to Hardy's study. "This will give us an alternative approach."

The fact that two research groups converged on the same gene gives experts confidence in the findings. Both studies were published online Wednesday in the New England Journal of Medicine.

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