The Role of Neuroinflammation in Alzheimer’s Disease: A Systematic Literature Review (P7-9.013)

This systematic literature review (SLR) aimed to investigate the role of neuroinflammation in AD and explore the association of neuroinflammation with AD disease progression. Several mediators of neuroinflammation can serve as therapeutic targets for Alzheimer's disease (AD) and as prognostic biomarkers. A SLR was conducted in 2023 using MEDLINE®, Embase®, and PsycInfo® databases to identify English-language articles from 2012 on AD including mild cognitive impairment (MCI). Two independent reviewers screened titles and examined full-text records for relevance. The SLR identified 3669 articles, of which 114 were included, and detailed data were extracted from 56. Cerebrospinal fluid (CSF) inflammatory biomarkers - YKL-40, sTREM2, and GFAP were identified to have a key role in AD neuroinflammation. Significantly higher levels of CSF YKL-40, CSF sTREM2, and CSF GFAP were found in patients with dementia due to AD compared with cognitively unimpaired control subjects. CSF sTREM2 changes were found to be sensitive to preclinical stages of AD and showed prognostic value in predicting rate of cognitive decline in AD. CSF YKL-40 levels were higher in the dementia stage of AD and increased longitudinally in patients with all-cause MCI and AD patients with dementia; highest baseline levels of CSF YKL-40 in subjects with all-cause MCI predicted progression to dementia due to AD. In cognitively unimpaired/people with subjective cognitive decline, higher baseline levels of serum or plasma GFAP predicted steeper rate of cognitive decline and clinical progression to AD dementia. In AD patients with dementia, higher levels of plasma GFAP were associated with greater change in MMSE score and poor cognitive outcome during follow-up. Evidence from fluid biomarkers consolidates the role of neuroinflammation in pathophysiology of AD and supports clinical use of GFAP for prognostic purpose as recommended in the draft NIA-AA Revised Criteria for Diagnosis and Staging of Alzheimer's Disease 2023 guidelines. Disclosure: Prof. Heneka has nothing to disclose. Dr. Gauthier has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TauRx . Dr. Gauthier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly Canada . Dr. Gauthier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai . Dr. Gauthier has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ENIGMA USA. Dr. Gauthier has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AmyriAD. Dr. Gauthier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medesis. Dr. Gauthier has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzheon. Dr. Gauthier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Karuna. Dr. Gauthier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Otsuka . Dr. Gauthier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NovoNordisk. Dr. Gauthier has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen Canada. Dr. Gauthier has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Sharon Francis Foundation . Dr. Gauthier has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JPAD. Dr. Gauthier has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Lundbeck Foundation . Dr. Gauthier has received publishing royalties from a publication relating to health care. Dr. Chandekar has received personal compensation for serving as an employee of Novo Nordisk A/S. Dr. Chandekar has stock in Novo Nordisk A/S. Mrs. Hviid Hahn-Pedersen has received personal compensation for serving as an employee of Novo Nordisk A/S. Mrs. Hviid Hahn-Pedersen has stock in Novo Nordisk. Dr. Bentsen has received personal compensation for serving as an employee of Novo Nordisk. An immediate family member of Dr. Bentsen has stock in Novo Nordisk. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Abbvie. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Acumen. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for AlzPATH. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Annexon. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Apellis. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Fujirebio. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Siemens Healthineers. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions.