• Alois Alzheimer, the German psychiatrist for whom the disease is named, first described the characteristic plaques and tangles of the disease through an autopsy of a brain. Until the eighties, many considered Alzheimer’s disease a normal part of aging.
• With more funding and the invention of new scientific techniques, Alzheimer’s disease was theorized to be caused by an “amyloid cascade,” where aggregates of the brain protein amyloid-beta are overproduced and become the main cause of neurodegeneration. For many sufferers, the aggregation is caused by an abnormal gene passed down through families. However, late-onset sporadic cases of Alzheimer’s disease-those with all the signs of the disease but without a genetic basis-has complicated the “amyloid cascade” theory into an ongoing debate. Today, this is the most common type of Alzheimer’s disease.
• Scientists began to unravel the genetic causes of Alzheimer’s disease by looking at several faulty genes. A gene on chromosome 21, called the APP gene, encodes a precursor to the amyloid-beta plaques implicated in Alzheimer’s disease. Individuals with Down syndrome have an extra copy of chromosome 21 and are more likely to be afflicted. Mutations in the gene that codes the protein presenilin, involved in the cleavage of the APP precursor into amyloid-beta, are also key contributors to Alzheimer’s disease.
Treatment for Alzheimer’s disease appeared in the nineties. Donepezil, the first Alzheimer’s disease drug, was approved for use in 1997. The drug works by maintaining high levels of acetylcholine, a neurotransmitter, to help memory function despite the destruction of brain cells due to the disease.
• Research targeting amyloid-beta and its precursors has progressed in mice models of Alzheimer’s disease. U of T scientists recently identified a drug that prevents amyloid-beta from aggregating in mice showing Alzheimer’s disease symptoms. The drug prevented any additional cognitive damage the disease would have caused if allowed to progress. Another drug, Flurizan, is in phase 3 clinical trials and works by lowering levels of plaque precursors.
For Alzheimer’s disease researchers, stem-cell therapies, prevention mechanisms (like lowered caloric intake) and genetic screens are among today’s priorities. However, there are still a number of unanswered questions-for instance, the role of the “tangles” Alzheimer first observed in 1906. With modern tools like the MRI, studying and diagnosing neurodegeneration is no longer done as Alois Alzheimer did a century ago, on the autopsy table.