Scientists from the University of Pittsburgh found neuroinflammation is the key driver of the spread of pathologically misfolded proteins in the brain and causes cognitive impairment in patients with Alzheimer’s disease.
They showed in living patients that neuroinflammation—or activation of the brain’s resident immune cells, called microglial cells—is not merely a consequence of disease progression; rather, it is a key upstream mechanism that is indispensable for disease development.
The research suggests that combination therapy aimed to reduce amyloid plaque formation and limit neuroinflammation might be more effective than addressing each pathology individually.
Alzheimer’s disease is characterized by the accumulation of amyloid plaques—protein aggregates lodged between nerve cells of the brain—and clumps of disordered protein fibers, called tau tangles, forming inside the nerve cells.
Although studies showed ample evidence that microglial activation drives the spread of tau fibers in Alzheimer’s disease, this process has never been proven in humans.
In the study, the team used live imaging to look deep into the brains of people with various stages of Alzheimer’s disease and healthy aging people.
They found that neuroinflammation was more prevalent in older people and that it was even more pronounced in patients with mild cognitive impairments and those with Alzheimer’s disease-associated dementia.
Bioinformatics analysis confirmed that tau propagation depended on microglial activation—it is a key element that links the effects of amyloid plaque aggregation to tau spread and, ultimately, cognitive impairment and dementia.
The study findings suggest that targeting neuroinflammation might be beneficial for people with early-stage Alzheimer’s disease and that it might help reverse or at least slow down the accumulation of pathologic tau protein in the brain and stave off dementia.
The team says many elderly people have amyloid plaques in their brains but never progress to developing Alzheimer’s disease.
The results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to widespread brain damage and cognitive impairment.
If you care about Alzheimer’s disease, please read studies about a new biomarker of Alzheimer’s disease, and these two old drugs may help treat Alzheimer’s disease.
For more information about brain health, please see recent studies about why some older people are less likely to have Alzheimer’s disease, and results showing this daily habit may help treat Alzheimer’s disease.
The research was published in Nature Medicine and conducted by Tharick Pascoal et al.
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