Alzheimer's research: The setup and setbacks
A select timeline of research, discovery, salesmanship and spending. Said Zaven Khachaturian, a former director of Alzheimer's research at the National Institute on Aging: 'Every major pharmaceutical company put money into the amyloid idea, and they all failed because the idea was flawed ... It became gradually an infallible belief system ... that's not very healthy for science when scientists ... accept an idea as infallible. That's when you run into problems.'
German psychiatrist Alois Alzheimer describes "plaques and tangles" in the brain of a middle-aged woman with dementia.
April: A journal editorial by neurologist Robert Katzman argues that most senility in older adults is Alzheimer's disease, until then diagnosed only in people under age 65.
May: Robert Butler, director of the new National Institute on Aging, promotes the expanded definition of Alzheimer's disease.
The Alzheimer's Disease and Related Disorders Association is created by Butler and others to advocate for federal research dollars.
The protein in Alzheimer's brain plaques is isolated and named amyloid beta.
Zaven Khachaturian at the NIA proposes counting plaques at autopsy to confirm a diagnosis of Alzheimer's disease.
The protein in Alzheimer's brain tangles is identified as tau.
Four labs identify the bigger protein that produces amyloid beta.
Amyloid hypothesis is proposed: amyloid beta plaque triggers Alzheimer's disease.
The first mutation causing early-onset Alzheimer's disease is located on a gene involved in producing amyloid beta.
Researchers put an Alzheimer's genetic mutation in mice, creating important but imperfect models of the disease.
FDA approves Aricept, the first cholinesterase inhibitor drug for Alzheimer's disease. These drugs don't slow underlying mental decline.
Elan pharmaceutical company's amyloid beta vaccine clears brain plaque in mice.
Labs identify enzymes that cut amyloid beta from the bigger protein. Pharmaceutical companies start developing pills to block them.
Amyloid beta vaccine abandoned when it causes brain swelling in people.
Studies of anti-inflammatory drugs show no effect or halt early over heart concerns.
Plaque is detected for the first time in living people, confirmed in first amyloid beta PET scan study. Scans later show plaque doesn't correlate with cognitive decline.
Pharmaceutical companies start testing amyloid antibodies in people with Alzheimer's.
The first drug to target amyloid beta, tramiprosate, performs no better than placebo in slowing mental decline.
The amyloid vaccine cleared plaque, but didn't help cognition, according to first published brain autopsies of participants.
Eli Lilly's enzyme inhibitor pill is discontinued when it lowers amyloid beta but causes skin cancer and accelerates cognitive decline.
July: Amyloid antibody bapineuzumab fails to slow Alzheimer's decline, a blow to Johnson & Johnson and Pfizer.
August: Eli Lilly's amyloid antibody solanezumab fails to slow Alzheimer's, but a possible effect in people with mild symptoms convinces the company to launch another big study.
Eli Lilly halts its study of another enzyme inhibitor pill due to abnormal liver tests. Roche stops a study of a similar drug without explanation.
People with no cognitive problems start taking anti-amyloid drugs in studies funded jointly by government and pharmaceutical companies to see if striking earlier prevents symptoms.
Hype surrounds initial results from a small study of Biogen's amyloid antibody aducanumab.
July: First drug to target the tangle protein tau fails in a clinical trial.
November: Eli Lilly's second big trial of solanezumab in people with mild Alzheimer's symptoms fails.
Merck stops a study of its enzyme inhibitor pill after it lowers amyloid beta but doesn't help cognition. A second study of the same drug is stopped a year later for making cognition worse.
January: Pfizer ends internal research for Alzheimer's and Parkinson's drugs and slashes 3000 positions in its neuroscience program.
April: A new definition of Alzheimer's disease is based only on brain changes, primarily amyloid plaque. People no longer need to have thinking or memory problems to have Alzheimer's.
January: Roche stops study of its anti-amyloid drug in people with early Alzheimer's.
March: Biogen pulls plug on aducanumab, the fourth failure of a big amyloid antibody study.
September: Safety concerns prompt Biogen and Eisai to halt a study of its enzyme inhibitor pill designed to lower amyloid beta, the last in a string of similar studies stopped early.
Results expected from the study of anti-amyloid drugs in people who have mutations for early-onset Alzheimer's disease.