Alzheimer’s Experts Share Diverse Insights on Disease
Some 5.4 million Americans have Alzheimer’s disease, and given longer lifespans ahead, “we’re facing quite a crisis,” David M. Holtzman said during a recent AAAS event intended to stimulate new thinking and speed medical advances. The number of Alzheimer’s patients is likely to triple within 50 years, but researchers still can’t detect the disease until it’s too late to prevent dementia and death, said Holtzman of the Washington University School of Medicine in St. Louis (WUSTL).
Yet, optimism prevailed 6 April as researchers spoke to a packed AAAS auditorium about “Breaching Barriers in Alzheimer’s Disease.” Reisa Sperling of Brigham and Women’s Hospital and Massachusetts General Hospital announced a proposal for a new clinical trial. Other speakers described insights into amyloid plaque formation in the brain—a hallmark of the disease—as well as genetic factors, imaging techniques, and lessons from other neurodegenerative diseases.
Late-onset Alzheimer’s disease, affecting people who are 60 or older, accounts for 99% of all cases. Although much rarer, the early-onset familial form can be especially devastating, striking those as young as 30. “Age and family history are the biggest risk factors,” explained WUSTL’s Alison Goate. “Even though genes are playing a role, that’s not all it is,” she said. A number of disease-causing genetic mutations as well as the risk factor apolipoprotein E4 have been identified.
Remaining physically active can promote overall good health, Sperling said, but avoiding Alzheimer’s isn’t as simple as playing Sudoku. As Mark Mintun of Avid Radiopharmaceuticals noted, a gene-environment interaction seems likely. Two radiotracers, combined with PET scanning, make it possible to visualize amyloid plaques, he said. Cerebrospinal fluid analysis can also be used to detect the plaque components tau and amyloid-beta 42 peptide, but Holtzman said high levels probably signal advanced deterioration, even if cognitive symptoms are mild.
An array of presentations offered support for the amyloid hypothesis, which assumes that amyloid-beta peptide is the key culprit in plaque formation. But Mathias Jucker of the Hertie Institute for Clinical Brain Research and the University of Tübingen also posed unconventional questions, such as whether environmental factors may trigger plaque formation. Steven Finkbeiner of the Gladstone Institute of Neurological Disease asked whether neuroinflammation may be a common thread among various neurodegenerative diseases. Don W. Cleveland of the University of California, San Diego urged looking beyond neurons to assess the role of other brain cells.
Richard Ransohoff of the Cleveland Clinic offered intriguing clues to the function of nonneural cells called microglia and a microglia modulator, the fractalkine receptor, which seems to affect disease outcomes. Andrew Dillin of the Salk Institute for Biological Studies described an aging “toggle switch” that might help prevent diseases that involve protein misfolding. Sperling proposed a trial to “test the hypothesis that interfering with amyloid accumulation upstream will affect downstream neurodegeneration.”
The public event, supported by The Agouron Institute, honored the late Science editor emeritus and AAAS senior advisor Philip Hauge Abelson. A related workshop, chaired by Marc Tessier-Lavigne of The Rockefeller University and Tom Maniatis of Columbia University Medical Center, will result in a white paper in Science Translational Medicine.