Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Microglial activation and tau propagate jointly across Braak stages
We previously published about this research in a story titled “How Neuroinflammation Drives Alzheimer’s Progression” which can be found here. The study was originally published in the scientific research journal Nature Medicine. You can view the abstract of the study here.
The research team was affiliated with the University of Pittsburgh School of Medicine.
What Happened?
There is still a lot that the scientific community doesn’t understand about Alzheimer’s disease. However, neuroinflammation is a known sign of the illness. Scientists previously had concluded that neuroinflammation was a result of the progression of the disease. However, compelling evidence from studies that have used animal models of Alzheimer’s and cultured cells in the lab setting has suggested that neuroinflammation in the form of microglial activation spurs the development of tau fibers.
These fibers play a role in the appearance of amyloid plaques in the brain, protein clumps that are a key aspect of the development and detection of Alzheimer’s. The findings from this study sought to determine if the evidence demonstrated in prior cell culture and animal model studies could be decisively duplicated in human subjects. A total of 130 patients participated in the study. This group comprised patients across the age and disease progression spectrum of Alzheimer’s.
The brains of these patients were examined using positron emission tomography in order to search for tau fibers, amyloid beta plaques, and microglial activation. Network analysis demonstrated that tau and microglial activation correlated with each other while following a Braak-like pattern or stage. Using regression analysis, the scientists determined that the propagation of tau was dependent on the microglia network.
Overall, the team found that the presence of tau, along with interaction between amyloid-beta and activated microglia, were the strongest predictors of cognitive impairment in the study group. In addition, the interactions between activated microglia and amyloid-beta allowed for the spread of tau along Braak stages. Neuroinflammation was most prevalent in the oldest participants and in those with dementia or mild cognitive impairment.
About Alzheimer’s Disease
Alzheimer’s disease, often just called Alzheimer’s, is a neurodegenerative illness affecting the brain that is primarily characterized by memory loss and dementia, which progressively worsens over time. Alzheimer’s disease is the leading cause of dementia around the world, linked to around 70 percent of cases. The cause of this disease isn’t clear, but a family history of the disease, particularly in the patient’s parents, appears to be the dominant risk factor. Other possible factors may include high blood pressure, depression, and head injuries. Memory decline is often the first recognized symptom; others include mood swings, disorientation, and difficulty speaking; these symptoms worsen over time to the extent that the person cannot function in daily life; paranoia, aggression, and then apathy are common. Treatment is symptomatic and supportive, and no known medications can halt disease progression. Life expectancy following diagnosis is between three to nine years. To learn more about Alzheimer’s disease, click here.
Why Does it Matter?
The results from this study have implications for how the medical and scientific communities understand the disease mechanism and progression for Alzheimer’s. Gaining a greater understanding of how the illness progresses will be critical for the development of effective treatment, an effort that so far has seen only very limited success. There is no cure for Alzheimer’s disease and current treatments are not able to prevent the illness from worsening.
With this understanding, researchers are also beginning to shift their views regarding how Alzheimer’s could best be treated as well:
“Our research suggests that combination therapy aimed to reduce amyloid plaque formation and limit neuroinflammation might be more effective than addressing each pathology individually.” – Tharick Pascoal, MD, PhD, lead author and assistant professor of neurology and psychiatry
Additionally, specifically trying to address neuroinflammation in people with early-stage disease could be an effective approach that could help slow down or even possibly reverse the spread of tau fibers and therefore limit or erase the impacts of dementia.
“We know that amyloid accumulation on its own is not enough to cause dementia—our results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to wide-spread brain damage and cognitive impairment.”
