Research Updates

The Search for New Ways to Treat Alzheimer's Disease

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.

Alzheimer's Genome Project Pre-publication Summary


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.

The Cure Alzheimer's Fund National Alzheimer's Disease Research Strategy

Prepared by:

Rudolph E. Tanzi, Ph.D.
Chairperson, Cure Alzheimer’s Fund Research Consortium
Joseph P. and Rose F. Kennedy Professor of Neurology
Harvard Medical School,
Director, Genetics and Aging Research Unit,
MassGeneral Institute for Neurodegenerative Disease
Department of Neurology
Massachusetts General Hospital
114 16th Street
Charletown, MA 02129

Timothy W. Armour
President and CEO
Cure Alzheimer’s Fund
34 Washington Street Suite 300
Wellesly Hills, MA 02481

The overarching goal of a national AD research strategy is to reach a cure most efficiently by accelerating studies aimed at identifying and characterizing all of the genes that influence susceptibility to AD, placing highest priority on those that will most readily lead to effective therapeutics for the treatment and prevention of AD.

Over the next decade, the influx of roughly 50 billion dollars into AD research should allow us by 2020 to identify all of the genes involved in AD susceptibility, and to arrive at a cure based largely on prevention.

Research Papers Supported By Cure Alzheimer's Fund

This is a list of papers funded by Cure Alzheimer's Fund. It also includes “layperson” descriptions of each paper. We are grateful to the researchers for translating the work of their papers into language more accessible to most of us than the more precise technical language useful to them and their peers.

We thank all the researchers and lab personnel for their dedication and commitment to the common mission of ending this disease, and we congratulate all of them for the important work reflected in these papers.

We also are grateful to all of those who literally made this work possible. Without those of you who have supported Cure Alzheimer’s Fund projects through your generosity, these papers and the forward momentum they represent would not exist.


Major Findings Linking New Genes to Alzheimer's Disease Announced in Publication of Four Papers

Four papers published this fall in leading science journals refer to the identification of new genes that confer risk for, or protection against, Alzheimer’s disease.