Brain Inflammation Identified as Culprit in Alzheimer’s Symptoms

Researchers from the University of Pittsburgh School of Medicine, as reported in JAMA Network Open, have identified that common neuropsychiatric symptoms observed in Alzheimer’s disease patients may originate from brain inflammation rather than the traditionally implicated amyloid and tau proteins.

This groundbreaking finding not only contributes to the understanding of Alzheimer’s disease progression but also opens new avenues for the development of therapies targeting the neurological symptoms associated with the condition. Neuropsychiatric symptoms such as irritability, agitation, anxiety, and depression are notoriously challenging to manage in Alzheimer’s patients.

These symptoms lack a clear cause and pose significant challenges for families providing care. Cristiano Aguzzoli, M.D., a postdoctoral associate at the University of Pittsburgh and the first author of the study, notes the difficulty in controlling these symptoms and highlights the impact they have on the caregivers’ ability to support their loved ones effectively. 

The researchers built on earlier work conducted in 2023, where scientists at the University of Pittsburgh identified excessive brain inflammation as a critical factor in initiating Alzheimer’s disease and predicting the risk of developing symptoms in cognitively unimpaired elderly individuals. This prior research suggested the importance of neuroinflammation in the pathological cascade involving key players like amyloid beta and tau. 

The current study provides compelling evidence that brain inflammation is a direct cause of the neuropsychiatric symptoms often accompanying Alzheimer’s-associated dementias. In their investigation, the researchers worked with 109 elderly individuals, most of whom had no cognitive impairments but tested positive for amyloid and tau. 

Utilizing brain imaging to measure levels of neuroinflammation, amyloid beta, and tau, and comparing these results with clinical assessments of neuropsychiatric symptom severity, the researchers identified a strong association between microglial activation (a marker of neuroinflammation) and various neuropsychiatric symptoms, including disturbed sleep and agitation.

While amyloid and tau levels alone predicted neuropsychiatric symptoms, the presence of neuroinflammation had an additional impact. Notably, neuroinflammation was most strongly associated with caregivers or family members reporting rapid mood swings in their loved ones, a common symptom of Alzheimer’s disease.

Individuals whose caregivers experienced higher levels of distress when caring for them exhibited greater levels of brain inflammation. This study adds to the growing body of evidence highlighting the role of brain inflammation in the early stages of Alzheimer’s disease progression, where symptoms like excess irritability tend to emerge.

Additionally, it suggests that clinical trials focusing on neuroinflammation as a preventive therapy for Alzheimer’s could monitor neuropsychiatric symptoms to assess treatment effectiveness. Conversely, drugs targeting neuroinflammation could potentially help reduce the severity of neuropsychiatric symptoms, offering relief to caregivers and improving overall patient support.

Senior author Tharick Pascoal, M.D., Ph.D., an associate professor of psychiatry and neurology at the University of Pittsburgh, emphasizes the broader implications of their findings by noting the collaboration with scientists worldwide to extend these insights to other types of dementia, including Parkinson’s dementia, where both neuroinflammation and neuropsychological abnormalities are found. 

Journal Reference  

Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.45175.