Alzheimer’s Disease: Current State and Hope for the Future

author: Li-Huei Tsai, Howard Hughes Medical Institute
published: Oct. 7, 2010,   recorded: May 2009,   views: 3329

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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 enrichment…by 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.

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