Post-mortem studies of the brains of women with Alzheimer’s disease (AD) show a much lower estrogen content than similar women without the disorder, researchers report.

The findings may help explain the higher prevalence of AD in women than men, since animal experiments show brain estrogen deficiency accelerates the brain “plaque” build-up that characterizes the disease.

Blood estrogen analysis did not support the brain tissue findings, since serum estrogen was low in both the AD patients and normal subjects, Dr. Rena Li and colleagues at the University of Chicago note in the Proceedings of the National Academy of Sciences.

Li told Reuters Health that “brain estrogen deficiency is more specific than blood estrogen deficiency” in the development of AD. “That is the key finding - the brain can’t manufacture estrogen.”

To examine the correlation between brain tissue findings and the onset and severity of AD, Li’s team conducted animal studies in which they crossed mice lacking an estrogen-synthesizing enzyme with mice carrying a protein related to AD plaque build-up.

The resulting animals had greatly reduced brain estrogen levels and early onset plaque formation. By contrast, mice that underwent ovary removal did not develop estrogen-deficient brain disease.

Li said the findings in these “ovariectomized” mice support the fact that not all post-menopausal women develop AD. “It is brain-specific…and may have a genetic basis,” she explained.

She said potential treatment of AD with estrogen therapy would require drug formulations that cross the tissue barrier that separates blood from the brain. Her team is currently screening a number of natural estrogen products to assess their ability to cross this barrier.

SOURCE: Proceedings of the National Academy of Sciences, December 19, 2005.