In Alzheimer's Patients, Neuropsychiatric Symptoms Correlate with Neuroinflammation
Chronic, unresolved inflammation is a feature of aging. It emerges from mitochondrial dysfunction and mislocalization of mitochondrial DNA, from visceral fat tissue, from senescent cells, and from a range of other maladaptive processes. Sustained inflammatory signaling is disruptive of cell and tissue function. In recent years, researchers have come to put a greater emphasis on the role of chronic inflammation in the onset and progression of Alzheimer's disease. While it remains the case that protein aggregation (of altered amyloid-β and tau) is the primary point of focus in Alzheimer's research and the development of treatments, inflammation does appear to have a central role in the pathology of the condition.
Earlier this year, scientists discovered that excessive brain inflammation is critical for disease initiation and can predict whether cognitively unimpaired elderly are at a higher risk of developing Alzheimer's symptoms. This earlier research hinted at the importance of neuroinflammation in the pathological cascade involving other key players in Alzheimer's pathology including amyloid beta and tau. Now new findings provide the first strong evidence that brain inflammation is also a direct cause of neuropsychiatric symptoms that often accompany Alzheimer's-associated dementias.
In the new study, the researchers worked with 109 elderly individuals, the majority of whom had no cognitive impairments. Most of those individuals were, however, positive for amyloid and tau. By measuring levels of neuroinflammation, amyloid beta, and tau via brain imaging and comparing the results with clinical assessments of neuropsychiatric symptom severity, the scientists discovered that microglial activation was strongly associated with a variety of neuropsychiatric symptoms, including disturbed sleep and agitation. While levels of amyloid and tau alone were predictive of neuropsychiatric symptoms, neuroinflammation seemed to have an added effect.
Neuroinflammation was most strongly associated with caregivers or family members reporting their loved one's rapid mood swings from calm to tears or anger, one of the common symptoms of the disease. Individuals whose caregivers showed higher levels of distress when caring for them had greater levels of brain inflammation. Taken together, the study adds to the growing evidence of the role of brain inflammation in the early stages of the disease progression, when symptoms like excess irritability tend to emerge. It also suggests that clinical trials targeting neuroinflammation as a preventive therapy for Alzheimer's could track neuropsychiatric symptoms as one way of measuring the treatment's effectiveness. Conversely, drugs specifically targeting neuroinflammation could potentially help reduce neuropsychiatric symptom severity and alleviate some of the psychological burden experienced by caregivers, thus improving patient support.
Link: https://www.upmc.com/media/news/112723-alzheimers-brain-inflammation