Background

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly and a burgeoning unmet medical need that will only worsen as the average lifespan continues to increase. The prevalence of AD increases with every decade after the age of 60 and ~ 20% of the population can expect to get this devastating disease in their lifetime given the current average lifespan of  ~78 years. AD is strongly influenced by inherited factors. In fact, after age, the greatest risk factor for AD is family history. Studies of several thousand pairs of twins have revealed that at least 80% of Alzheimer’s disease involves the inheritance of risk-conferring gene defects—either gene mutations that directly cause the disease, or gene variants that increase susceptibility. To date, we know the identity of four AD genes. Over the last two decades, studies of these four genes, and particularly the three early-onset AD genes co-discovered by Cure Alzheimer’s Fund Research Consortium Chairperson, Dr. Rudy Tanzi, have guided virtually all laboratory research aimed at understanding AD and developing novel therapeutics. As invaluable as the known AD genes have been to solving the mystery of AD and guiding new therapeutic interventions, these four genes account for only 30% of the inheritance of Alzheimer’s disease. While the three early onset AD genes (APP,PSEN1, and PSEN2) account for roughly half of familial early-onset AD, for the most common late-onset (>60 years) form of AD, only one gene has thus far been established to increase susceptibility. This gene is known as the apolipoprotein E (APOE) gene. Since the discovery of the association between AD risk and the E4 variant of the APOE gene, increasing evidence indicates that this variant is neither sufficient nor necessary to cause the disease. We know that APOE works together with other genes to influence one’s inherited risk for AD. To date, the identity of the additional AD genes, which account for 70% of the genetic basis of AD, has remained unknown. 

By John R. Cirrito, Ph.D., and David M. Holtzman, M.D.
Microdialysis Core Facility, Department of Neurology, Hope Center for Neurological Diseases, Washington University, St. Louis, MO

A major contributing factor in Alzheimer’s disease is the elevation of a protein called amyloid-β, or Aβ. Since high levels of Aβ play a role in the disease, many research groups around the world are developing therapies designed to lower the levels of this protein. With the help of Cure Alzheimer’s Fund, our group initiated an ambitious project to discover new drugs that reduce Aβ levels. Our approach is to test drugs in living animals (mice). While this process is time-consuming, it enables us to discover entirely new classes of compounds that traditional drug screening methods typically might overlook. 

Supplemental Information for Senate Special Committee on Aging Hearing

Introduction

Alzheimer’s disease (AD), the most common form of dementia, was first described roughly one hundred years ago in Bavaria by Dr. Alois Alzheimer in his presentation of an early-onset (<60 years) case.  AD is a progressive and fatal neurodegenerative disease that impairs memory and overall cognition. There are more than 5 million documented patients according to best estimates, with some experts suggesting that may be only 20% of the total number actually affected. The number of new cases grows by more than 10% per year. Alzheimer’s disease is the seventh leading cause of death for people of all ages, the fifth leading cause of death in people age 65 and older, and is the only one of the major diseases (heart disease, breast and prostate cancer and stroke) to be increasing in mortality; up almost 33% from 2002 to 2004. Medicare expenditures for Alzheimer’s and other dementias in 2005 were $91 billion; this total is projected to increase to $160 billion by 2010. State and federal Medicaid spending for nursing home care for people with Alzheimer’s and other dementias was estimated at $21 billion in 2005, and is projected to increase to $24 billion by 2010. Given these estimates and no significant containment or decrease in Alzheimer’s, Medicaid and Medicare expenses for Alzheimer’s and related dementias will be approximately $184 billion by 2010, or approximately 27% of the entire combined anticipated expenditure for Medicare and Medicaid in 2010.