Our work should provide important information on why older individuals are so vulnerable to neurodegenerative diseases. And we'll try to define the therapeutic targets that are most important for older patient populations
—Mel B. Feany
DISEASES THAT CAUSE the degeneration of nerve cells in the brain – “Neurodegenerative diseases” – exact a devastating toll on aging populations in the US and increasingly, throughout the world. Alzheimer’s disease is the world's most common and most feared form of dementia. It is estimated to affect more than about 5.3 million people in the United States, roughly one in eight Americans over the age of 65. The global prevalence of Alzheimer’s disease will also escalate worldwide as populations age and life expectancies increase. Although early-onset forms of the disease, usually linked to specific genetic mutations, can occur in people in their 30s, 40s or 50s, Alzheimer's disease is overwhelmingly an illness of aging. Dementia — more than half of which is caused by Alzheimer's disease — affects about 10% of people older than 65, but nearly half of those aged 85. The symptoms typically begin with mild forgetfulness and, in the course of a decade, progress to complete incapacitation, unless death intervenes first. The economic and social costs are high (the cost of treating people with Alzheimer’s and other dementias is likely to exceed $170 billion in 2010), but the emotional toll on affected families is incalculable. Studies of Alzheimer's disease and other widespread neurodegenerative diseases are an important component of The Ellison Medical Foundation research agenda.
Alzheimer’s disease has two main pathological hallmarks: Excessive amounts of the protein β-amyloid (Aβ or amyloid-beta) clump together to form plaques between cells in the brain; and the protein tau twists to form neurofibrillary tangles within neurons. These accumulations gradually prevent the normal functions of nerve cells and cause them to die. Research interest in amyloid plaques has been particularly intense, with researchers working to elucidate how and why elevated β-amyloid levels occur and how they affect brain function. Many of The Ellison Medical Foundation's grantees in this area are studying how β-amyloid is formed from a larger protein, the amyloid precursor protein or APP. Simply put, this process involves proteins called secretases that act as "molecular scissors" to cut out or cleave β-amyloid from APP. Proteins called presenilins also play a role in APP processing. Many of the rare early-onset forms of the disease result from mutations in genes that control APP processing. The hope is that understanding this pathway in its full complexity will lead to control of Aβ deposition, which could have enormous value in preventing or treating Alzheimer's disease.
Alzheimer’s disease is one of a group of neurodegenerative diseases caused by the buildup of toxic proteins that damage brain tissue. Parkinson’s disease, Huntington’s disease and other conditions also feature accumulation of “mis-folded” and improperly processed proteins, although the specific proteins and affected regions in the brain differ among these conditions. For this reason, research aimed at understanding the causes of each of these diseases can provide important insights that may be helpful in treating or preventing other serious diseases of the aging nervous system, and perhaps, in understanding and ultimately staving off the decline of brain function associated with typical aging in the absence of overt neurodegenerative disease.