DIMENSIONS Spring 2005

ADVANCES IN AD RESEARCH: A TIMELINE

by Julie Cleveland

The UW ADRC’s participation in these advances is indicated by bold print.

• 1700s – The word “dementia” came into use as a legal and medical term.
• 1901 – Neuropsychiatrist Dr. Alois Alzheimer wrote a case history about 51-year-old patient Auguste D., describing her clinical symptoms of dementia, which he termed “presenile” dementia.
• 1906 – An autopsy of patient Auguste D. showed neurofibrillary tangles and amyloid plaques in the brain, the hallmark changes in the brain associated with Alzheimer’s disease (AD). Amyloid plaques are clumps of protein fragments that accumulate outside of the brain’s nerve cells. Tangles are twisted strands of another protein that form inside brain cells.
• 1910 – Psychiatrist Emil Kraepelin coined the term Alzheimer’s disease.
• 1920s to 1930s – Amyloid plaques were discovered in the brains of young adults with Down’s syndrome. Subsequent research would show that Down syndrome patients, who have an extra copy of chromosome 21, are at risk to develop AD in their late 30s and 40s.
• 1930s to 1950s – Psychiatrist David Rothschild wrote numerous articles advocating that underlying personality was important in diagnosising and treating AD. This spurred an interest in psychiatric and other therapeutic treatments for older patients with dementia.
• 1963 – The first successful electron microscopic studies of the AD brain were completed by R.D. Terry and M. Kidd, advancing knowledge of physiological changes in the brains of persons with AD.
• 1965 – G. Blessed, B. Tomlinson, and M. Roth presented the first studies comparing scores on a memory and concentration test in persons with dementia to the subsequent number of amyloid plaques in their brains at autopsy. Their work provided the first convincing evidence that AD was a common cause of dementia in older, as well as younger, adults.
• 1974 - The National Institute on Aging was established, and AD was finally recognized as a real disease and a growing health problem.
• 1979 - The Alzheimer’s Association became a national organization for the support of individuals with AD and their families.
• 1984 – The National Institute on Aging estabsslished the five original Alzheimer’s Disease Re-search Centers (ADRCs). The University of Washington ADRC began the following year. Today, there are 32 centers.
• 1991 – The first gene mutation directly implicated in AD was discovered – the amyloid precursor protein (APP) gene on chromosome 21. Research has shown that mutation in the APP gene leads to one form of early-onset (pre-senile) AD.
• 1993 – Cognex (trade name for tacrine) was the first drug approved by the Food and Drug Administration (FDA) to treat cognitive symptoms of AD. Due to possible side effects, including liver damage, it is rarely prescribed today.
• 1995 – Transgenic mouse models were developed for AD, improving researchers’ ability to study the disease.
• 1995 – A second gene mutation related to early-onset Alzheimer’s disease was discovered – the presenilin 1 (PS1) gene.
• 1995 – A third gene mutation associated with early-onset AD, presenilin 2 (PS2), was discovered by ADRC researchers, Drs. Gerard Schellenberg, Thomas Bird, Ellen Wijsman, and their colleagues.
• 1995 – Former president Ronald Reagan announced he had been diagnosed with AD, and he and his family became strong supporters of AD research.
• 1996 – Apolipoprotein-E (APOE) was identified as a susceptibility gene for the more prevalent late-onset form of AD.
• 1996 – Aricept (donepezil) was approved by the FDA to treat cognitive symptoms in mild to moderate AD.
• 2000 – Excelon (rivastigmine) was approved by the FDA to treat cognitive symptoms in mild to moderate AD.
• 2001 – Reminyl (galantamine) was approved by the FDA to treat cognitive symptoms in mild to moderate AD.
• 2003 – Namenda (memantine), the first drug for the treatment of moderate to severe AD, was approved by the FDA. Unlike earlier drugs that increase acetylcholine in the brain, memantine appears to work by regulating the activity of glutamate, one of the brain’s specialized messenger chemicals involved in information processing, storage, and retrieval.