Alzheimer’s Disease

among the most feared diagnoses in medicine, Alzheimer’s disease represents a personal and societal tragedy of enormous proportions. Every 72 seconds, someone is diagnosed with Alzheimer’s.

Scientists have long recognized that a subtle loss of small numbers of nerve cells (neurons) occurs normally in the human brain in later life. But brain cells in individuals who develop AD deteriorate more rapidly. A central goal of the Foundation’s research has been to discover the cause of this premature brain cell degeneration. Important clues have emerged from the striking changes in brain structure first described in 1907 by Alois Alzheimer, a German psychiatrist. In a microscopic postmortem study of the brain of a woman who had experienced progressive and severe cognitive loss, Alzheimer noted curious abnormalities: “senile plaques” (collections of degenerating nerve cell endings) and “tangles” (bundles of twisted filaments inside nerve cells).

About 25 years ago, scientists found that the centers of these senile plaques are made of abnormal deposits of a protein called amyloid-ß (Aß). The Foundation’s scientists went on to discover that the Aß protein making up these amyloid deposits is also a normal metabolic product made by virtually all cells in our body throughout life. But in the brains of patients with Alzheimer’s disease, the protein builds up excessively, due in part to faulty genes that either over-produce or fail to remove the protein. The situation seems akin to hardening of the arteries, where a normal metabolite—cholesterol—builds up excessively in certain blood vessels.

We are studying precisely how the Aß protein is made and released from living cells and how to decrease its production or increase its removal. What is most exciting is that discoveries already made by Foundation scientists are now being used worldwide to discover drugs that block the production, or enhance the removal, of the Aß protein in the brains of Alzheimer victims. Some of these agents have already entered clinical trials in typical Alzheimer patients.

Multiple Sclerosis

multiple sclerosis (ms) is a chronic, debilitating disease that strikes tragically in the prime of life—often between 20 to 40 years of age. In MS, the body’s immune system eats away at the protective myelin sheath that covers nerves, interrupting communication between the brain and the rest of the body. A wide variety of symptoms may occur including, commonly, numbness, blurred vision, and decreased coordination. Symptoms may be mild or severe, and they progress unpredictably and differently in each person with the illness. MS is challenging both to diagnose and to treat, but new therapies and advances in research are increasingly encouraging.

Recent studies indicate that the most probable cause of the disease lies within the immune system. For reasons not clearly understood, the body seems to attack its own healthy tissue. Cells that normally fight infection—T lymphocytes, B lymphocytes and macrophages—give up their usual protective roles and instead destroy the myelin sheath, thereby blocking or disrupting the flow of impulses traveling along nerves.

FDA-approved treatments are beginning to produce a reduction in the number of attacks MS patients experience and a slowing of disease progression. New approaches include immune therapy designed to stimulate regulatory T-cells that shut down disease-inducing immune cells; treatments aimed at rebuilding myelin; and drugs that protect the immune system.

The Foundation’s scientists are looking to develop treatments to be given at the very first sign of MS to halt disability and disease progression, as well as to find better therapies for the early stages of the disease. Another of the research team’s urgent aims is to identify a treatment for progressive MS. Importantly, our research group is, for the first time, investigating the possibility of developing a vaccine to prevent multiple sclerosis.

Parkinson’s Disease

many of us are familiar with the symptoms of Parkinson’s disease (PD): slowness in initiating movements, a shuffling gait and a resting tremor. With as many as 60,000 new cases a year, Parkinson’s is the second most common neurodegenerative disease, after Alzheimer’s.

Drugs like l-dopa and certain surgical treatments can temporarily improve symptoms but do not slow the progressive, debilitating loss of the neurons that make dopamine in the brain.

The Foundation’s scientists are searching for the underlying causes of this selective neuronal loss and are identifying mechanistic steps that could be blocked by potential drug treatments. The National Institutes of Health (NIH) has acknowledged our scientific progress in PD by naming us a Morris K. Udall Parkinson’s Disease Center of Excellence, one of only a handful in the United States.

New hopes for disease-slowing treatments have emerged from studies of families in which relatively rare but aggressive forms of PD are inherited. Several genes have been identified that produce early-onset disease when they have mutated. The proteins made by these genes are attractive targets for novel drugs that could help prevent neurodegeneration in PD. One of the faulty genes encodes a protein, ∂-synuclein, which is the major component of Lewy bodies, the characteristic nerve cell deposits of PD.

These findings suggest a general connection between the processes that lead to PD and Alzheimer’s diseases. Both are characterized by abnormal fibrous protein deposits (Lewy bodies and amyloid plaques, respectively), which occur in severely affected areas of the brain. Drugs that block protein fibrilization could potentially slow or even prevent these diseases.