Work described in this story was made possible in part by federal funding supported by taxpayers. At Harvard Medical School, the future of efforts like this - done in service to humanity - now hangs in the balance due to the government's decision to terminate large numbers of federally funded grants and contracts across Harvard University.
- By STEPHANIE DUTCHEN
What is the earliest spark that ignites the memory-robbing march of Alzheimer's disease? Why do some people with Alzheimer's-like changes in the brain never go on to develop dementia? These questions have bedeviled neuroscientists for decades.
Now, a team of researchers at Harvard Medical School may have found an answer: lithium deficiency in the brain.
The work, published in Nature, shows for the first time that lithium occurs naturally in the brain, shields it from neurodegeneration, and maintains the normal function of all major brain cell types. The findings - 10 years in the making - are based on a series of experiments in mice and on analyses of human brain tissue and blood samples from individuals in various stages of cognitive health.
The scientists found that lithium loss in the human brain is one of the earliest changes leading to Alzheimer's, while in mice, similar lithium depletion accelerated brain pathology and memory decline. The team further found that reduced lithium levels stemmed from binding to amyloid plaques and impaired uptake in the brain. In a final set of experiments, the team found that a novel lithium compound that avoids capture by amyloid plaques restored memory in mice.
The results unify decades-long observations in patients, providing a new theory of the disease and a new strategy for early diagnosis, prevention, and treatment.
Affecting an estimated 400 million people worldwide, Alzheimer's disease involves an array of brain abnormalities - such as clumps of the protein amyloid beta, neurofibrillary tangles of the protein tau, and loss of a protective protein called REST - but these never explained the full story of the disease. For instance, some people with such abnormalities show no signs of cognitive decline. And recently developed treatments that target amyloid beta typically don't reverse memory loss and only modestly reduce the rate of decline.
It's also clear that genetic and environmental factors affect risk of Alzheimer's, but scientists haven't figured out why some people with the same risk factors develop the disease while others don't.
Lithium, the study authors said, may be a critical missing link.
