Alzheimer's disease is strongly driven by chronic inflammation in brain tissue. Studies in which senescent, inflammatory microglia are removed from the brain strongly suggests this to be the case in the later stages of the condition. Here, researchers use animal models to demonstrate that it may also be the case in the early stages, prior to onset of obvious symptoms of cognitive decline. A view of Alzheimer's disease in which inflammation is the dominant mechanism - resulting from some combination of exposure to pathogens, accumulation of senescent cells, and dysregulation of immune cells due to amyloid-β aggregates - is gathering support these days.
In a new animal study examining Alzheimer's disease, researchers found that disease progression could be slowed by decreasing neuroinflammation in the brain before memory problems and cognitive impairment were apparent. The new findings point to the importance of developing therapies that target very early stages of the disease. In 2011, the National Institute on Aging updated the diagnostic criteria for Alzheimer's disease to reflect its progressive nature. The criteria added a preclinical stage during which brain changes are taking place, but the person is still asymptomatic and, therefore, unaware of his condition. Biomarker profiles could eventually be used to identify people in the disease's early stages who might benefit from early treatments.
"Starting an intervention at the earliest stage of the disease, when cellular and molecular alterations have already been triggered but major damage to the brain has not yet occurred, could offer a way to reduce the number of people who go on to develop full Alzheimer's dementia. However, there have been few studies in animals examining therapeutic strategies that target timepoints before symptoms can be seen."
The researchers designed an animal study to gain a deeper understanding of the role of neuroinflammation in Alzheimer's disease during the pre-symptomatic stage of the disease, which might represent the best time for therapeutic intervention. The study results suggest that rebalancing neuroinflammation in animals that show altered neuroinflammatory parameters could be beneficial. "Our results help demonstrate that neuroinflammation in Alzheimer's disease is an extremely complex phenomenon that can change over the disease's progression and varies based on factors such as affected brain area. We hope that these findings will prompt scientists to further investigate neuroinflammation at the earliest stages of the disease, which may represent an important pharmacological target."