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Future Research and Questions Surrounding GFAP, sTREM2 in Alzheimer Disease: Lynn Bekris, PhD

SAP Partner | <b>Cleveland Clinic</b>

The molecular biologist at the Cleveland Clinic Lerner Research Institute provided insight on the lingering questions about GFAP and sTREM2 astrocytes, and their immunologic correlations with Alzheimer disease and related dementias. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"We can look at levels of amyloid, tau, and neurodegeneration, and determine when this ratio, for example, might be most altered. Is it altered when amyloid is positive, but when tau is negative? Is it altered when people have α-synuclein at a highly elevated level—which we think would be true because of the relationship between α-synuclein and soluble TREM2, but we don’t know that yet?"

In an effort to better distinguish dementia with Lewy bodies (DLB) from Alzheimer disease (AD), researchers at Cleveland Clinic decided to explore differences in cerebrospinal fluid (CSF) levels of both soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and glial fibrillary acidic protein (GFAP). sTREM2, a myeloid cell activity marker, has been genetically linked to AD risk, while GFAP, an astrocyte activity marker, has been linked to astrogliosis in several neurologic disorders. Led by Lynn Bekris, PhD, the study included individuals clinically diagnosed with AD, DLB, mild cognitive impairment (MCI), Parkinson disease (PD), and cognitively normal controls (CN).

Between the groups, significant differences (P <.0001) for sTREM2 were found for CN vs DLB and AD vs DLB, and significant differences for α-synuclein were found for CN vs DLB. The P-value for α-synuclein vs GFAP in entirety was also significant (P = .0258) which was driven by the significant P-value for the DLB patient group (P = .0517). Additionally, for α-synuclein and sTREM2, the entire cohorts were found to be strongly correlated (P <.0001), driven by the significant correlation for all the patient groups except CN.

Bekris, a molecular biologist at the Cleveland Clinic Lerner Research Institute, sat down with NeurologyLive® to discuss the findings and how they can be expanded on. She provided detailed descriptions as to the questions that remain following the study, the importance of the measures observed, and why sTREM2 has sustainable use in clinical settings. Additionally, she answered questions about data regarding the MCI stages, and whether increased CSF levels were expected.

1. Jain L, Khrestian M, Tuason ED, et al. 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). Presented at: 2022 Alzheimer’s Association International Conference; July 31 to August 4; San Diego, CA. 68332