Leon J. Thal, MD, Chair of the Department of Neurosciences at UCSD since 1993, died tragically in a plane crash on February 3, 2007 near Borrego Springs, California. He was 62 years old.

A visionary and pioneer in the study of Alzheimer's Disease (AD), Dr. Thal was Director of the Alzheimer's Disease Cooperative Study (ADCS) and the Alzheimer's Disease Research Center (ADRC). He joined the Department of Neurosciences in 1985 as an Associate Professor and was promoted to full Professor in 1989. He was named Chair in 1993.

After obtaining his medical degree (summa cum laude) at Downstate Medical Center in New York , Dr. Thal interned at Kings County Hospital before pursuing a neurology residency and additional fellowship training at Albert Einstein College of Medicine. He continued as a faculty member at Albert Einstein until 1985, when he accepted an appointment as Associate Professor of Neurosciences at UCSD. He was promoted to Professor in 1989 and awarded the Florence Riford Chair in Alzheimer’s Disease. He became Chair of the Department of Neurosciences in 1993, serving with distinction until his untimely death in 2007.

Dr. Thal conducted research in three domains: clinicopathological and behavioral studies of dementia, clinical trials in Alzheimer’s disease (AD), and enhancement of neuronal function and regeneration. He was Principal Investigator of the Alzheimer’s Disease Research Center (ADRC). The ADRC is recognized for improving the diagnosis and assessment of dementia patients and for major contributions to the neuropathological and genetic determinants of dementia.

Clinicopathological and Behavioral Studies of Dementia:
Several important observations resulted from a series of studies using clinical data and tissue from the ADRC. The ADRC was one of the first groups to call attention to the presence of Lewy bodies in the brains of patients with AD, a pathological marker associated with Parkinson’s disease. The ADRC demonstrated that choline acetyltransferase (ChAT) activity, a marker of cholinergic neurons, is decreased not only in AD but also in the Lewy body variant (LBV) of AD, Parkinson’s disease, and in patients with diffuse Lewy body disease. The ADRC is now focusing on the identification of subjects with mild cognitive impairment, a precursor of dementia, participation in multi-center treatment trials, and development of biomarkers for early detection of AD.

Alzheimer’s Disease Cooperative Study and Instrument Development:
Dr. Thal served as Principal Investigator of the Alzheimer’s Disease Cooperative Study (ADCS), a multi-site project composed of over 80 sites. The ADCS was established in 1991 and has enrolled over 3,600 subjects in either clinical or instrument trials in the United States and Canada . To date, the ADCS has initiated 21 protocols (18 drug trials and 3 instrument protocols) ranging from phase I to phase III studies. On several occasions, the ADCS has conducted trials that have a high public profile. For example, the ADCS demonstrated that high-dose vitamin E delays the time to a composite endpoint of death, institutionalization, loss of basic activities of daily living, and progression of dementia in patients with moderately advanced AD. This therapy is now widely used in the United States and abroad. The ADCS has spearheaded development of the concept of mild cognitive impairment, a state where individuals have a memory deficit but do not meet current clinical criteria for AD. The ADCS has developed new instruments for measuring cognition, activities of daily living, and global functioning in patients with AD. These instruments are fully validated. They have been distributed free of charge to over 350 investigators worldwide, and one or more or these instruments are being used in almost all ongoing AD clinical trials.

Enhancement of Neuronal Function and Regeneration:
The Thal group is responsible for the development of a more specific technique for lesioning the cholinergic system using an immunotoxin 192 IgG-saporin, which binds to nerve growth factor (NGF) receptors, and results in cholinergic cell loss. Gene therapy has been used to restore cholinergic functioning in animals using genes that deliver NGF or choline acetyltransferase, the synthetic enzyme for acetylcholine.

Dr. Thal's many honors include the Arthur Cherkin Memorial Award in 2003, and the Potamkin Prize for Research in Pick’s, Alzheimer’s, and Related Diseases in 2004. In December 2004, Governor Arnold Schwarzenegger appointed Dr. Thal to serve on the Independent Citizens Oversight Committee of the California Institute for Regenerative Medicine. He also served on the National Institute of Aging Advisory Council.

Dr. Thal was a frequent reviewer and consultant for the NIH as well as the National Science Foundation and Veterans Administration. He served as a permanent advisor on the FDA anti-dementia assessment team. In addition, he served on the Editorial Boards of Alzheimer Disease Review, Current Alzheimer Research, Dementia and Geriatric Cognitive Disorders, Drug Discovery Today, International Journal of Geriatric Psychopharmacology, Journal of Molecular Neuroscience, Journal of Neural Transmission, and Neurobiology of Aging and Neurodegenerative Diseases. He was an ad hoc reviewer for Annals of Neurology, Archives of Neurology, Brain Research, Neurology, Nature, New England Journal of Medicine, and Proceedings of the National Academy of Sciences.

links:
Shiley-Marcos Alzheimer’s Disease Research Center
Alzheimer's Disease Cooperative Study