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Alzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic Strategies

Christopher M. Clark, MD, and Jason H.T. Karlawish, MD

4 March 2003 | Volume 138 Issue 5 | Pages 400-410

Alzheimer disease is a complex neurodegenerative dementing illness. It has become a major public health problem because of its increasing prevalence, long duration, high cost of care, and lack of disease-modifying therapy. Over the past few years, however, remarkable advances have taken place in understanding both the genetic and molecular biology associated with the intracellular processing of amyloid and tau and the changes leading to the pathologic formation of extracellular amyloid plaques and the intraneuronal aggregation of hyperphosphorylated tau into neurofibrillary tangles. The identification of disease-causing autosomal dominant mutations as well as gene polymorphisms that alter the risk for pathology indicate that Alzheimer disease is a genetically complex disorder. This progress in our understanding of the molecular pathology has set the stage for clinically meaningful advances in diagnosis and treatment. Emerging diagnostic methods that are based on biochemical and imaging biomarkers of disease-specific pathology hold the potential for accurately diagnosing Alzheimer disease at the earliest stage of the illness—the time when disease-modifying treatment will be most effective. Currently available cholinesterase inhibition therapy targets the cognitive symptoms. However, the goal of new therapies under development is halting the pathologic cascade and potentially reversing the course of the disease. If these new therapies are successful, they will represent a remarkable medical advance for patients and the families who care for them.

Author and Article Information

From the University of Pennsylvania, Philadelphia, Pennsylvania.

Grant Support: By National Institute on Aging (NIA) grants AG10124 and AG09215. Dr. Karlawish was funded by a Paul Beeson Fellowship and by NIA grants K01-AG00931 and P01-AG10124.

Corresponding Author: Christopher M. Clark, MD, Memory Disorders Clinic, Penn-Ralston Center, the University of Pennsylvania, 3615 Chestnut Street, Philadelphia, PA 19104.

Potential Financial Conflicts of Interest: Dr. Clark has been a paid participant in advisory board meetings for Janssen Pharmaceutica, Parke-Davis, Eisai, and Elan (formerly Athena Neurosciences). He has received honoraria from Parke-Davis, Eisai, and Pfizer for giving educational presentations on the diagnosis and treatment of Alzeheimer disease. Dr. Clark has also participated in research studies sponsored by Elan, Eisai, and Parke-Davis. Dr. Karlawish has received an educational grant from Ortho-McNeil.

Current Author Addresses: Drs. Clark and Karlawish: Memory Disorders Clinic, Penn-Ralston Center, University of Pennsylvania, 3615 Chestnut Street, Philadelphia, PA 19104.

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