Postmortem brain study suggests that increased microglial function in the brain may be a protective factor in Alzheimer’s disease

By David G. Amaral, Ph.D., and Lilliam Acosta-Sanchez, MPH

Alzheimer’s disease is a progressive brain disorder that affects a person’s memory and ability to do daily activities. It’s a condition that advances with age. According to the Alzheimer’s Association, Alzheimer’s disease is the most common type of dementia, accounting for 60-80% of dementia cases. First discovered in the early 1900s by Dr. Alois Alzheimer, Alzheimer’s disease is characterized by the presence of plaques and tangles in the brain during autopsy.

Researchers in the Division of Neuropathology at Johns Hopkins University analyzed postmortem brain samples from individuals with Alzheimer’s disease and healthy age control matches donated to Johns Hopkins Alzheimer’s Disease Research Center (ADRC) and the Baltimore Longitudinal Study of Aging (BLSA) to look at why some individuals with typical Alzheimer’s brain plaques and tangles do not develop dementia. They hoped to determine what the protective factors may be.

The researchers found that in the brains of people with asymptomatic (not showing symptoms of the disease) Alzheimer’s disease, their cognitive function was not affected. This means that they didn’t develop dementia even though plaques and tangles were present at autopsy. When analyzing the tissue samples, the researchers found that in asymptomatic cases, there was an increase in microglia around the plaques and tangles, suggesting that microglial cells may have an impact on decreased plaque accumulation in the brain, thereby protecting the brain of the asymptomatic person from cognitive decline or developing dementia. Microglia are a type of brain cell that helps keep our brains healthy by constantly scanning and removing damaged cells. They are the brain’s primary immune cells and play a role in the development of brain connections. The researchers concluded that if this mechanism could be better understood, enhancing it through medical intervention may prevent or slow the cognitive impacts of Alzheimer’s disease.

While more studies are needed, the findings from this study are an excellent example of how essential postmortem brain donations are to advance our knowledge of how the brain functions, the mechanisms and molecular changes that lead to Alzheimer’s disease, in this case, and other neurodevelopmental disorders, such as autism. Without the analysis of postmortem brains, the investigators would not be aware of the protective effects of the microglial cells. Knowledge from these postmortem brain studies can help researchers understand the progression of age-related and neurodevelopmental disorders, identify individuals at a higher risk of developing these disorders, improve diagnosis, and develop new interventions that could enhance the quality of life for individuals affected by them.