New BU Prof Offers Hope for Alzheimer's

Early detection technology could slow disease's progress

By Vicky Waltz

Lee E. Goldstein is on a quest to eradicate Alzheimer’s disease, and he’s racing the clock. “The disease will bankrupt the U.S. health-care system if we don’t intervene soon,” he says. “We simply won’t have the resources to handle the number of people who develop the disease.”

The key, says Goldstein — who is joining the faculty at BU’s School of Medicine in the departments of psychiatry, ophthalmology, neurology, pathology, and laboratory medicine and the College of Engineering in the department of biomedical engineering — is early detection. And based on a chance discovery, Goldstein and his colleagues are developing a laser-based diagnostic technology that will detect the disease years — and possibly decades — before the first symptoms emerge.

Goldstein, formerly an assistant professor of psychiatry at Harvard Medical School and the director of the Molecular Aging and Development Laboratory and the Center for Biomedical Metallomics at Brigham and Women’s Hospital, has brought his research team to BU to continue their work at two new state-of-the-art research facilities, one located at the BioSquare Research Park on the Medical Campus and the other at the BU Photonics Center on the Charles River Campus. Goldstein is also joining the research faculty at the Photonics Center.

“My team and I are honored to join the Boston University community,” Goldstein says. “The research dynamism at BU affords very powerful, complementary support for our interdisciplinary translational neuroscience research.” Members of Goldstein's research team include Mark Burton, Noel Casey, Joy Ghosh, Anca Mocofanescu, Juliet Moncaster, and Weilan Xu.

Alzheimer’s disease, the leading cause of dementia and the seventh-leading cause of death in the United States in 2004, according to the Alzheimer’s Association, occurs when sticky, tangled plaques containing deposits of the protein fragment beta-amyloid build up between nerve cells in the brain. Four years ago, Goldstein and his research team determined that this amyloid protein also collects in the lens of eyes in people afflicted with Alzheimer’s disease and causes an unusual cataract that is completely different from common age-related cataracts. The findings were published in the British medical journal The Lancet.

“I was working with Alzheimer’s mice,” he says, “and I noticed they were developing dense bilateral cataracts in their eyes.” Healthy control mice, on the other hand, showed no signs of cataracts. Goldstein then looked at the eyes of people with Alzheimer’s disease and found the same cataracts. The discovery established the first evidence of Alzheimer’s-linked pathology outside the brain, and led Goldstein and his colleagues to develop a laser-based diagnostic technology that searches for amyloid protein buildup in the eyes and could aid in early detection of the disease.

“Alzheimer’s is an exceedingly slow disease that starts many years to a decade or more before the beginning of cognitive decline,” Goldstein says. “With the emerging treatments coming on line, we can beat back this disease, but only if we begin treatment early, long before the onset of clinical symptoms. If we can combine emerging new treatments with early detection, we can beat this disease and do so soon."

Goldstein hopes that in another three years or so, adults will be able to ask their physician for a laser-based molecular diagnostic screening test for Alzheimer’s disease. Six years ago, he cofounded Neuroptix Corporation, an Acton-based biotech company that is spearheading lead-edge laser technology for detection of abnormal accumulation of the beta-amyloid proteins in the lens of the eye — the same proteins that cause brain-cell death in Alzheimer’s patients — using a laser eye-scanning device and eye drops.

“Our most recent work suggests that we may be able to detect the disease at the molecular level from the earliest stages of the disease, hopefully well before the first clinical symptoms," Goldstein says. "Once you show the classic signs of Alzheimer’s — forgetfulness or disorientation — it’s the beginning of the end. That’s why early detection is so crucial. We want to stop it before it starts.”

Goldstein is also driven by personal experience with the disease and its effects: around the time he discovered the connection between Alzheimer’s and cataracts, Goldstein’s father-in-law was diagnosed with frontotemporal dementia (FTD), a rare and particularly brutal neurodegenerative disease that affects the frontal and temporal lobes of the brain — the areas generally associated with personality and behavior.

“I’m a geriatric psychiatrist and a neuroscientist by training,” he says, “and my research is driven by a passionate desire to help my father-in-law, my patients, and my patients’ families.”

Vicky Waltz can be reached at vwaltz@bu.edu.

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