It’s been a century since Alois Alzheimer first spotted the plaques and tangles inside the brain of his patient, Auguste D. Our understanding of the disease that bears his name has since grown considerably, much of it in recent decades. But even as scientists around the world scrutinize the various aspects of this baffling disease, myriad mysteries remain. What exactly is the cause of Alzheimer’s?
Which comes first, the plaques or the tangles? How can we diagnosis it better and earlier, in the stages when people seem to respond better to treatments? What can we do to treat the disease and to slow its progression? And dare we even begin to dream of the day when we can cure Alzheimer’s and spare millions of people from the ravages of this disease?
The quest to answer these questions has intensified in recent years as baby boomers gradually enter their mid 60s. At the current rate, experts predict that by the year 2030—when the entire baby boomer generation will be over the age of 65—the numbers of people with Alzheimer’s will increase to 7.7 million from its current figure of 4 million. By the year 2050, those numbers could be as high as 13.2 million. With the current cost of caring for people with Alzheimer’s estimated between $50 billion to $100 billion, the future costs look ominous—unless the disease can be delayed, prevented, or cured.
With the amount of research now going on, scientists are optimistic that something will happen to slow the trend. Federal funding for Alzheimer’s research reached an all-time high in 2004 of $679 million, according to the Alzheimer’s Association. A search for “Alzheimer’s” on the search engine at www.clinicaltrials.gov, the federal government’s Web site on current clinical trials, turned up fifty-four studies alone. The energy and effort being applied to a better understanding of this disease is clearly reaching a fever pitch. Here, we will examine some of the current research that is giving hope to families and patients around the world afflicted by Alzheimer’s.
PINPOINTING THE GENES
Figuring out what sets the disease process in motion is one of the mysteries about Alzheimer’s that has puzzled scientists for years. Studies have demonstrated that genetics play a role in the disease. For instance, we already know that people who have early-onset Alzheimer’s tend to have a strong family history for the disease. Scientists have discovered that people who have early-onset Alzheimer’s Disease have mutations—unexpected changes in a single gene or in sections of chromosomes—in one of three genes. Meanwhile those with late-onset Alzheimer’s Disease were likely to carry a variant of a gene called apolipoprotein E epsilon-4, or APOE-4.
Experts believe that like many other diseases, Alzheimer’s develops from a complicated mix of genetic factors and environmental influences. Identifying the genetic risk factors could help predict an individual’s risk for developing Alzheimer’s. Genetics could also help researchers develop new drugs to slow the course of the disease.
To identify the genes that cause Alzheimer’s Disease, the National Institute on Aging is collecting genetic material from families with several members who have late-onset Alzheimer’s, the kind that develops after age 60. The NLA and the National Alzheimer’s Association are working with investigators at Indiana University’s National Cell Repository for Alzheimer’s Disease and Columbia University. The Alzheimer’s Disease Genetics Study, as the study is formally called, will include information on 1,000 families.
Genetics are only part of the answer. Not everyone who has a family member with Alzheimer’s Disease will get Alzheimer’s, and not everyone who has Alzheimer’s Disease can always identify a relative who had the disease. Figuring out what puts one gene carrier at risk while another is free of disease is another avenue of research.
GETTING AN EARLIER DIAGNOSIS
Experts believe that the biological processes underlying the development of Alzheimer’s start years before any symptoms are apparent. They also know that early diagnosis offers the greatest hope for preventing or delaying the disease. But how do we know that someone is in the process of developing Alzheimer’s? What are the biological changes? Several studies are providing information that experts hope will lead to new diagnostic tools that will allow earlier detection of Alzheimer’s.
Nano-sized Markers
One type of technology that offers hope for an earlier diagnosis is nanoscale technology. Imagine dividing up a human hair into 50,000 parts on its diameter. Or dividing up a meter into a billion parts. That’s the size of a nanometer, which is a unit of measure some scientists are working with to pinpoint a protein associated with Alzheimer’s.
Using a technology called bio-barcode amplification, researchers at Northwestern University and Rush University Medical Center were able to measure the presence of a protein called amyloid (3-diffusible ligands, or ADDLs, in cerebrospinal fluid. Research has found that ADDLs appear in the earliest stages of Alzheimer’s before symptoms become apparent. ADDLs are only five nanometers wide and present in the cerebrospinal fluid at a very low concentration, making it hard to detect with conventional technology such as enzyme-linked immunoassays (ELISA) tests which are used to detect the presence of antibodies to make a diagnosis.
In a study, the researchers measured ADDL concentrations in thirty people. The concentration of ADDL was consistently higher in people diagnosed with Alzheimer’s than in those without the disease.
The bio-barcode technology offers hope that Alzheimer’s could be detected in its earliest stages, when treatments and preventive strategies might be most effective.
According to Chad Mirkin, one of the researchers at the Northwestern University Department of Chemistry and Institute for Nanotechnology: “This study is a major step forward in identifying a routine diagnostic tool for Alzheimer’s disease, and it validates our hypothesis that there are many biomarkers for disease that go under the radar of conventional diagnostic tools. The extraordinary sensitivity of the bar code assay has a chance to change the way the medical community thinks about molecular diagnostics and the markers they consider for many types of diseases.”
Adds colleague William Klein of the Northwestern University Institute for Neuroscience: “It’s a good bet that the very earliest stage of Alzheimer’s Disease memory loss begins when ADDLs attack key synapses in the brain. We predicted some of these ADDLs would leak into the cerebrospinal fluid, but until now we couldn’t detect them.
Thanks to the extraordinary sensitivity of the BCA, it’s been possible to validate the prediction, and maybe even set the stage for creating the first clinical lab test for Alzheimer’s disease.”
A Five-Year Plan
In another effort to identify better diagnostic tools, the National Institute on Aging has joined together with other federal agencies, private companies and organizations to launch a $60 million, five-year effort called the Alzheimer’s Disease Neuroimaging Initiative.
The study is an attempt to find changes in the brain that suggest the development of Alzheimer’s and can be detected by neuroimaging techniques such as serial magnetic resonance imaging (MRI) and positron emission tomography (PET). Prior studies show that PET scans can reveal that people with Alzheimer’s metabolize glucose at a slower rate in certain parts of their brain than people without the disease. Scientists will also be examining other biological markers for clues such as cerebrospinal fluid, urine, and blood. The 800 participants in the study will be cognitively normal, have MCI, or be in the early stages of Alzheimer’s Disease. Researchers will track their progress over two to three years.
A Special Compound
As of now, the only way to confirm a diagnosis of Alzheimer’s is at death, when an autopsy can reveal the telltale plaques and tangles that invade a brain afflicted with Alzheimer’s Disease. Scientists at the University of Pittsburgh Medical Center however, are perfecting a compound that will enable doctors to detect the presence of Alzheimer’s in someone’s brain while the patient is still alive.
The substance is being called Pittsburgh Compound B. By injecting it into patients, doctors will be able to confirm a person has Alzheimer’s and would eliminate some of the guess work involved in making a diagnosis. Perhaps even more important, the compound will help identify people at risk for the disease years before symptoms are evident. Experts know that brain changes may occur as much as thirty years before symptoms or signs emerge. Given that knowledge, patients may be able to start treatment early and prevent or delay symptoms of Alzheimer’s.
Pittsburgh Compound B (PIB) is designed to travel through the bloodstream, enter the brain, and attach itself to beta-amyloid deposits. PIB can then be detected by positron emission tomography (PET) scans. In a PET scan of the brain, areas with the greatest concentration of beta-amyloid should appear red and the area with no beta-amyloid should be blue.
Compound B may also have major implications in the development of drugs for the treatment of Alzheimer’s. With the use of Compound B, researchers will be able to assess and actually see the effectiveness of new medications designed to reduce amyloid deposits.
Scientists are still in the process of perfecting the substance. Many people who do not have Alzheimer’s, for instance, still have some amyloid in their brains. A compound that can distinguish that kind of amyloid from the destructive variety in Alzheimer’s will be important to identifying patients who have the disease.