human brain
Sean Cate
Sean Cate
April 3, 2024 ·  3 min read

Brain Autopsies Show Possible Culprit Behind Alzheimer’s Disease

Recent research led by the University of Washington has shed light on new potential workings of Alzheimer’s disease, offering us a glimpse into the workings of the brain’s immune system. The study, published in August, looks at the behavior of microglia, specialized immune cells crucial for maintaining brain health.1

A New Understanding

Microglia are responsible for clearing waste and preserving normal brain function and have been implicated in Alzheimer’s pathology. The study found that microglia in people with Alzheimer’s disease were often in a pre-inflammatory state, which potentially contributed to the disease’s progression. Katherine Prater, one of the lead researchers, highlighted the significance of these findings: “At this point, we can’t say whether the microglia are causing the pathology or whether the pathology is causing these microglia to alter their behavior.”

To better study microglia behavior, researchers used brain autopsy samples from both Alzheimer’s patients and healthy controls. Using advanced single-nucleus RNA sequencing techniques, they were able to identify distinct microglia clusters, with some types more prevalent in Alzheimer’s brains. These microglia exhibited gene expression patterns associated with inflammation and cell death.

Despite prior interests in targeting neuro-inflammation for Alzheimer’s treatment, clinical trials of anti-inflammatory medications yield limited success at this point. However, this study suggests that a better understanding of microglia behavior could pave the way for more effective therapeutic interventions.

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Steps in The Right Direction

The study’s lead neuroscientist, Kevin Green, emphasized the importance of further research: “Now that we have determined the genetic profiles of these microglia, we can try to find out exactly what they are doing and hopefully identify ways to change their behaviors that may be contributing to Alzheimer’s disease.”

These findings underscore the dynamic nature of microglia and their potential role in Alzheimer’s disease. By studying the overlap of immune cells and neurodegeneration, researchers may be able to develop targeted treatments that could minimize the effects of Alzheimer’s disease altogether.

In a separate study, researchers employed single-nucleus RNA sequencing to characterize microglia in Alzheimer’s brains with unprecedented depth. By enriching microglia nuclei, the researchers were able to identify distinct phenotypes associated with Alzheimer’s pathology.2 In other words, microglia play a multifaceted role in Alzheimer’s progression

Using advanced sequencing techniques, researchers uncovered major diversity in different microglia within Alzheimer’s brains. These findings provide valuable insight into how Alzheimer’s disease works and offer potential targets for future interventions.

Microglia and Alzheimer’s Disease

By dissecting microglia, researchers have identified subclusters specific to Alzheimer’s disease and additional potential regulators of microglia – which would affect the disease directly. These discoveries open new avenues for investigating the roles of microglia in Alzheimer’s disease and hold promise for the development of precision therapeutics.

These studies provide new, compelling evidence of microglia’s involvement in Alzheimer’s disease. By examining how microglia behave, researchers will be able to develop better intervention strategies that could slow or even halt the progression of this devastating disease.

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  1. Human microglia show unique transcriptional changes in Alzheimer’s disease.” Nature. Katherine E. Prater, Kevin J. Green, Sainath Mamde, Wei Sun, Alexandra Cochoit, Carole L. Smith, Kenneth L. Chiou, Laura Heath, Shannon E. Rose, Jesse Wiley, C. Dirk Keene, Ronald Y. Kwon, Noah Snyder-Mackler, Elizabeth E. Blue, Benjamin Logsdon, Jessica E. Young, Ali Shojaie, Gwenn A. Garden and Suman Jayadev. May 29, 2023.
  2. Brain Autopsies Suggest a New Culprit Behind Alzheimer’s Disease.” Science Alert. Rebecca Dyer. December 19, 2023.