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Anti-Inflammatory Agents: An Approach to Prevent Cognitive Decline in Alzheimer's Disease. J Alzheimers Dis 2022;85(2):457-472

Date

11/30/2021

Pubmed ID

34842189

DOI

10.3233/JAD-215125

Scopus ID

2-s2.0-85123281175   1 Citation

Abstract

Systemic inflammation is an organism's response to an assault by the non-self. However, that inflammation may predispose humans to illnesses targeted to organs, including Alzheimer's disease (AD). Lesions in AD have pro-inflammatory cytokines and activated microglial/monocyte/macrophage cells. Up to this point, clinical trials using anti-amyloid monoclonal antibodies have not shown success. Maybe it is time to look elsewhere by combating inflammation. Neuroinflammation with CNS cellular activation and excessive expression of immune cytokines is suspected as the "principal culprit" in the higher risk for sporadic AD. Microglia, the resident immune cell of the CNS, perivascular myeloid cells, and activated macrophages produce IL-1, IL-6 at higher levels in patients with AD. Anti-inflammatory measures that target cellular/cytokine-mediated damage provide a rational therapeutic strategy. We propose a clinical trial using oral type 1 IFNs to act as such an agent; one that decreases IL-1 and IL-6 secretion by activating lamina propria lymphocytes in the gut associated lymphoid tissue with subsequent migration to the brain undergoing inflammatory responses. A clinical trial would be double-blind, parallel 1-year clinical trial randomized 1a??:a??1 oral active type 1 IFN versus best medical therapy to determine whether ingested type I IFN would decrease the rate of cognitive decline in mild cognitive impairment or mild AD. Using cognitive psychometrics, imaging, and fluid biomarkers (MxA for effective type I IFN activity beyond the gut), we can determine if oral type I IFN can prevent cognitive decline in AD.

Author List

Brod SA

Author

Staley A. Brod MD Professor in the Neurology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alzheimer Disease
Animals
Anti-Inflammatory Agents
Biomarkers
Cognitive Dysfunction
Humans
Inflammation
Interferon Type I
Microglia
Randomized Controlled Trials as Topic