05/04/2009 2:00 PM 46"3002Li"Huei Tsai, Picower Professor of Neuroscience, Howard Hughes Medical Institute investigatorDescription: Measured in human suffering, and by statistics, Alzheimer's Disease (AD) presents a formidable specter: with incidence approaching 30 million worldwide and growing rapidly, it is now the sixth leading cause of death in the US. As life expectancy lengthens, AD is anticipated to triple in prevalence over the next few decades. The disease is found in nearly 50% of people age 85 and older. Triply higher medical costs are incurred by seniors with AD. These daunting facts give urgency and weight to molecular neuroscientist Li"Huei Tsai's research.
Tsai begins her presentation with an historical perspective of Alzheimer's, first documented in 1901 in Germany as "strange behavioral symptoms and loss of short"term memory." Post"mortem examination of a patient's brain showed "the hallmark pathological lesions: amyloid plaques and neurofibrillary tangles." Telltale manifestations include "forgetfulness, confusion, disorganized thinking, impaired judgment," difficulty expressing oneself, spatial and temporal disorientation, and incapacity in daily activities. Family members must often quit jobs to provide round"the"clock care. In the advanced disease, becoming bedridden engenders chronic infections, secondary conditions, and eventual demise.
Definitive clinical diagnosis can be elusive. Imaging techniques with radioactive tracers, using a compound that selectively binds with amyloid plaques, help to identify AD. Tsai describes several cognitive tests developed by fellow MIT researchers to aid in confirming the disease. One method assesses retention of verbal facts and geometric figures. Another diagnostic tool is functional MRI, pinpointing brain areas activated upon exposure to new versus repeated scenes, a challenge for memory. Both approaches reveal notable distinctions between AD patients and control subjects.
"Currently there is no treatment that can prevent, delay or reverse Alzheimer's Disease," says Tsai. FDA approved drugs that act upon neurotransmitters postpone cognitive deterioration by only a few months.
Using a transgenic mouse model, Tsai's pioneering research seeks to target compounds that can preferentially manipulate proteins to assume a desired structure. Resulting cellular differentiation into neurons could help correct deficits of AD by augmenting brain volume in specific regions, thereby enhancing learning and memory.
Just as experimental mouse subjects perform better with "environmental enrichmentby keeping them very physically engaged," Tsai recounts that "people with higher education, more active lifestyles" benefit cognitively as they age. As to the respective contributions of genetic and environmental factors, she believes "it's really a combination." Though treatment for Alzheimer's will not be solely pharmaceutical, Tsai hopes to identify chemical compounds to ameliorate the characteristic brain atrophy that robs one of vitality and dignity.
About the Speaker(s): Li-Huei Tsai initially embarked on a veterinary career in her native Taiwan in 1983, after receiving the D.V.M. degree from National Chung Hsing University. She soon moved to the U.S. to earn an M.S. at the University of Wisconsin, followed by a Ph.D. from the University of Texas Southwestern Medical Center at Dallas. She then joined Cold Spring Harbor Laboratory and Massachusetts General Hospital for postdoctoral training in the area of cancer research and cell cycle regulation. She was appointed Assistant Professor of Pathology at Harvard Medical School in 1994, where she refocused her research on brain development. She was elected investigator of Howard Hughes Medical Institute in 1997, and promoted to Professor of Pathology in 2002.
A major research interest of the Tsai lab is the mechanism leading to neurodegenerative diseases associated with cognitive decline and dementia such as Alzheimer's Disease. Recently, the Tsai lab has also made contributions to understanding the pathophysiology of neuropsychiatric disorders such as depression.
Tsai has won the Rita Allen Foundation Scholarship, Klingenstein Fellowship for Neurosciences, and Promising Investigator Award from Metropolitan Life Foundation.
Host(s): School of Science, Department of Brain and Cognitive Sciences

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