A cell-level map helps build an atlas of how the brain changes in Alzheimer’s
There is no escaping the difference between the brain of a person who has died from a neurodegenerative disease and a healthy person: In the case of severe Alzheimer’s, the brain will be noticeably smaller, with large gaps where pieces would normally nestle close together.
This shrinkage, known as brain atrophy, is brought on by the death of neurons and the connections they form throughout the entire cortex, the brain’s wrinkly outermost shell.
Nobody is aware of the causes of these profound changes in the brain that occur in Alzheimer’s disease, let alone how to halt or reverse them.
The Allen Institute’s neuroscientists and their associates, however, are concentrating on changes at a much smaller, granular scale in an effort to offer incredibly detailed insight into precisely what goes wrong in Alzheimer’s disease.
Using cutting-edge techniques to classify individual cells based on what their genes do, they have recently made some of the first data available to the public showing the precise types of neurons and other brain cells that die off or change in Alzheimer’s disease.
By preventing the death of these particular cell populations, this strategy may ultimately help to identify new targets for improved therapies that would be able to slow or stop the progression of the disease.
According to Ed Lein, Ph.D., Senior Investigator at the Allen Institute for Brain Science and leader of the Seattle Alzheimer’s Disease Brain Cell Atlas team, who published the new data, this method of mapping a diseased brain in cellular detail is only recently possible due to new techniques to study large numbers of individual brain cells.
The development of new tools to study the human brain has advanced to truly remarkable levels, and this has created entirely new avenues for the investigation of disease, according to Lein.
As these tools were being developed, it became clear that a much higher resolution atlas of what Alzheimer’s actually looks like at the cellular level could have a significant impact.
An introduction to Alzheimer’s
The Allen Institute serves as the hub of the National Institute on Aging-funded Seattle Alzheimer’s Disease Brain Cell Atlas consortium (SEA-AD), which also conducts research at Kaiser Permanente Washington Health Research Institute and UW Medicine.
The publicly accessible dataset includes detailed microscopy images of amyloid- and other disease-related proteins in the brains of 84 people who donated their brains to science after they passed away, as well as large-scale cellular and molecular information gathered from more than 1.2 million neurons and other brain cells.
The cellular methods applied by the consortium are based on earlier research conducted at the Allen Institute and elsewhere as part of the NIH-funded BRAIN Initiative, which uses genes activated in individual brain cells to classify them into distinct types.
These approaches are now being applied to understand Alzheimer’s disease at a new level of detail and resolution, having first been used to understand the fundamental cellular building blocks of a healthy brain.
The first of many data releases is this one. One of the researchers involved in the data release is Professor and Nancy and Buster Alvord Endowed Chair of Neuropathology at UW Medicine, C. Dirk Keene, M.D., Ph.D.
“My hope is that with this release and future releases, we will generate data that will give us clues as to how this disease actually works,” he said.
The likelihood that we will discover those drug targets and create drugs that work will increase as more scientists use novel approaches to try to understand the disease.
The list of Alzheimer’s brain components
The entire brain is not affected at once by Alzheimer’s disease. The entorhinal cortex is a part of the brain that is involved in memory, and as the disease progresses, it begins to affect nearby areas of the brain before killing all of the neurons in the cortex.
The middle temporal gyrus, which is affected roughly halfway through the course of Alzheimer’s progression, was the focus of the Seattle researchers’ first data release. Ultimately, they hope to understand the entire progression of the disease.
The 84 participants in the Adult Changes in Thought (ACT) study, a long-running study of brain aging led by Kaiser Permanente Washington and UW Medicine, or studies in the UW Medicine Alzheimer’s Disease Research Center, represent a spectrum across all stages of Alzheimer’s disease, from healthy aging to severe dementia.
The University of Washington School of Medicine BioRepository and Integrated Research (BRaIN) laboratory is in charge of organizing brain donations. Keene, who is in charge of the lab, calls brain donation “the greatest gift one can give to science, without which this research would not be possible.”