History of Alzheimers

History of Alzheimers Learning From Alzheimers On November 25, 1901, Dr. Alois Alzheimer, a 37-year-old neuropathologist and psychiatrist at the Hospital for the Mentally Ill and for Epileptics in Frankfurt, Germany, examined a female patient with an unusual mental illness. Her symptoms included memory loss, language problems, and delusional behavior. After the patient died in 1906, Alzheimer examined her brain and found strange formations of the amyloid plaques and tau tangles. Today, Alzheimers disease is the sixth-leading cause of death in the United States. People with Alzheimers progressively lose memory, language skills, and the ability to perceive time and space. The risk of developing Alzheimers also increases with age. Like PD, the underlying disease of Alzheimer starts decade or more before diagnosis. While the exact mechanism by which the disease spread isnt known, the pathology is driven by the aggregation of misfolded proteins either amyloid-beta plaques or tau tangles, or both with the damage spreading from neuron to neuron in a prion-like manner. Alzheimers researchers have recently developed some ingenious tools to help track the disease in the living brain. In 2002, Chester Mathis and the psychiatrist William Klunk developed the PET imaging method to detect and measure amyloid-beta deposition in the brain of living Alzheimers patients. The method involves injecting patients with a radioactive tracer that can penetrate the blood-brain barrier and bind selectively to the amyloid-beta protein. The detectors surrounding the patients head capture the radiation emitted by the tracer and convert them into a picture that represents the relative amounts of plaque buildup in different parts of the brain. PET imaging is an example of a biomarker, a metric that can quantify the progress of a disease in a living patient more sensitively than a clinical test like the UPDRS. No such imaging technique yet exists that can detect alpha-synuclein aggregates in the brains of people with PD. Other potential biomarkers are chemical assays that estimate the amyloid content in a patients cerebrospinal fluid, circulating blood, and urine. In the past decade, with the help of biomarkers, Alzheimers researchers have tested numerous drugs designed to target and break down amyloid-beta plaques. While some showed promise in open-label studies, they all failed when tested in phase 3 trials in patients with moderate to severe Alzheimers. One possible reason is that the drugs were given too late in the disease. To address that issue, Alzheimers researchers are working on three early-intervention studies. The first involves an extended family in South America. They are descendants from an individual who carried a rare mutation, called the Paisa mutation, for a heritable form of Alzheimers disease. By late 20th century, the mutation had spread to around 5,000 people in the city of Medellin. This Alzheimers kindred came to the attention of the University of Antioquia neuroscientist Francisco Lopera. A simple genetic screening test can determine which kindred members possessed the bad gene. Those individuals with the bad gene could be given anti-amyloid-beta drugs long before they showed any cognitive impairments. Loperas project is part of the Alzheimers Prevention Initiative headed by the psychiatrist Eric Reiman at the Banner Alzheimers Institute in Phoenix, Arizona. In the trial, the Paisa volunteers get a baseline cognitive assessment plus a biomarker evaluation (involving PET imaging, cerebrospinal fluid analysis, and other assays) to measure the distribution of amyloid beta. They are given Genentechs drug crenezumab, or a placebo. Researchers follow individuals for at least five years. A second genetic study also part of Banners Alzheimers Prevention Initiative involves 1,300 currently healthy individuals age 60 to 75 in Europe and North America. Members of this cohort are at high risk of developing Alzheimers because they have been identified as carrying two copies of a gene called apolipoprotein E4. Such people are not guaranteed to develop Alzheimers like carriers of the Paisa mutation, but their risk is extremely high. Study subjects will receive either a placebo or one of two experimental drugs developed by the Swiss pharmaceutical company Novartis. The third study, known as the A4 trials, is supervised by Dr, Reisa Sperling of Harvard Medical School. It involves a cohort of 1,000 healthy individuals age 70 or older. The individuals in the group exhibit normal cognitive abilities but also have higher than normal levels of amyloid-beta plaques in their brains as measured by a PET scan. This puts them at higher risk for developing Alzheimers. The question is, can that risk be reduced or eliminated? *** PD researchers require imaging and other biomarkers for alpha-synuclein that enable scientists to identify people and also to monitor the disease as it progresses. Chester Mathis and his colleagues are developing a radiotracer that will bind to alpha-synuclein and yield a PET image for PD. The PET tracer is just one element in a bigger Fox Foundation project the Parkinsons Progression Marker Initiative. The idea is to follow several groups of people forward in time performing clinical exams, taking biological samples, and doing multiple imaging scans along the way. Other researchers are looking elsewhere for Parkinsons biomarkers that might allow for early diagnosis. Kathleen Shannon and her colleagues at Rush University Medical Center accessed old colon biopsies performed during routine colonoscopy procedures for three individuals who went on to develop PD. Because these biopsies were done two to five years before the onset of the PD motor symptoms, they provided an opportunity to see if alpha-synuclein was present in the gut before motor symptoms emerged. Another possible place to look for alpha-synuclein is the submandibular gland. Charles Adler of the Mayo Clinic in Scottsdale, Arizona, biopsied the submandibular glands in twelve people with PD for more than five years and found Lewy pathology in nine of them. The British mathematician Max Little has developed computer algorithms to analyze human voice recordings to detect irregular patterns in PD patients. His PD Voice Initiative uses phone call data as potential biomarkers to diagnose and measure the progression of PD. Key Takeaways Alzheimers researchers have developed some ingenious tools to help track the disease in the living brain.To address the issue that the drugs were given too late in the disease in human drug trials, Alzheimers researchers are working on three early-intervention studies. Inspired by the Alzheimers researchers, PD researchers are working on multiple fronts to develop biomarkers to track PD in the living brain.