Cerebrospinal fluid glial fibrillary acidic protein (GFAP) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in Alzheimer's Disease and Related Dementias (ADRD). (20th December 2022)

• Record Type: Journal Article
• Authors: Jain, Lavanya; Khrestian, Maria; Tuason, Elizabeth D.; Pillai, Jagan A.; Rao, Stephen M.; Leverenz, James B.; Bekris, Lynn M.
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.068332
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Discerning Dementia with Lewy Bodies (DLB) from Alzheimer's disease (AD) can be a challenge for the clinician and represents a critical unmet medical need. Diagnosis of DLB is especially challenging in early stages due to variable core features and coexistent pathologies such as AD. A variable immune response has been implicated in AD/ADRD. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a myeloid cell activity marker, has been genetically linked to AD risk and glial fibrillary acidic protein (GFAP), an astrocyte activity marker, is liked to astrogliosis in a number of neurologic disorders. Our objective was to explore differences in cerebrospinal fluid (CSF) values of both sTREM2 and GFAP in AD/ADRD. This included individuals clinically diagnosed with AD, DLB, mild‐cognitive impairment (MCI), Parkinson's Disease (PD), and cognitively normal controls (CN). Method: Cohorts included participants from the Cleveland Clinic‐based Dementia with Lewy Body Consortium (DLBC), the Lou Ruvo Center for Brain Health Aging and Neurodegenerative Disease biobank (LRCBH‐biobank) and the Cleveland Alzheimer's Disease Research Center (CADRC). Patients were clinically characterized based on CSF biomarkers, clinical symptoms, and consensus review. Analytes measured included: CSF GFAP, CSF sTREM2, CSF a‐synuclein (aSyn) and plasma neurofilament light chain (NfL) using multiple platforms such as the Luminex/Millipore and Meso Scale Discovery systems. Result: In this AD/ADRD cohort, CSF aSyn was higher in MCI than both PD and DLB, while lower in DLB than CN and AD. CSF sTREM2 was higher in MCI, AD and DLB than CN. GFAP was higher in MCI than either CN or DLB, while AD was higher than DLB. sTREM2/GFAP ratio was higher in DLB than CN, MCI, AD and PD. Conclusion: These findings suggest that inflammatory factors, CSF sTREM2 and GFAP are altered in both AD and DLB. Future study of the relationship between CSF amyloid or tau and the immune response will help tease apart the potential influence of co‐existent AD‐related pathology on inflammatory factors in DLB. The findings will help inform possible immunotherapeutic strategies that seek to target the immune response in AD/ADRD.