Popular Alzheimer's theory may be false trail

"The research makes a very good case that these cells are subject to aging," said Smith, who did not participate in the study. "These cells were thought to be activated (against Alzheimer's), but this paper makes a strong case that they are not. The study has taken a novel approach that has led to a novel insight."

Using a commercially available antibody, Streit for the first time created a marker for microglial cells in human brain specimens that had been in chemical storage. The specimens were from 19 people with varying degrees of Alzheimer's, ranging from severe to none at all. Two of the samples were from Down syndrome patients, who are known to develop Alzheimer's pathology in middle age.

When researchers examined these cells alongside neurons under a high-resolution microscope, they found that — unless an infection had occurred elsewhere in the body — microglial cells from Alzheimer's patients were not distinctly larger or unusually shaped, which would have been the case had they been inflamed.

"What I expected to see is activated microglia right next to dying neurons," Streit said. "That is what I did not find. What I propose is glia are dying, and the neurons lose support. We now need to find out what caused glia to degenerate. Rather than trying to find ways to inhibit microglia with anti-inflammatory drugs, we need to find ways to keep them alive and strong. It's a whole new field."

The microglial cells had a tangled, fragmented appearance, similar to neurons in the throes of Alzheimer's disease or — old age.

"These cells are breaking into pieces," said Streit, who collaborated with Alzheimer's researcher Heiko Braak, M.D, of the Institute for Clinical Neuroanatomy in Frankfurt. "They are on their way out. For the first time, we are proving that microglial cells are subject to aging and may undergo degeneration, and that the loss of these cells precedes the loss of neurons. Research has been so focused on finding activated microglia, no one considered that these cells were degenerating and neurons lost support."

The work was supported by the National Institutes of Health, the German Research Council and the Evelyn F. and William L. McKnight Brain Institute.

Alzheimer's disease is the sixth leading cause of death in the United States and the fifth leading cause of death for Americans 65 and older, according to the Alzheimer's Association. The association estimates Alzheimer's and other dementias cost Medicare, Medicaid and businesses a total of $148 billion annually.