Increased transmembrane protein 119 (TMEM119) levels in the cerebrospinal fluid of patients with mild cognitive impairment due to Alzheimer's disease suggest early microglial involvement

Abstract

Introduction: We aimed to evaluate the potential of the microglial marker transmembrane protein 119 (TMEM119) in the cerebrospinal fluid (CSF) as a (differential) diagnostic biomarker for neurodegenerative diseases. Methods: Following assay validation, we used enzyme-linked immunosorbent assay to measure CSF TMEM119 in 174 patients from six diagnostic groups: Alzheimer's disease (AD, n = 35), amyotrophic lateral sclerosis (ALS, n = 33), cerebral microangiopathy (CM, n = 25), frontotemporal lobar degeneration (FTLD, n = 28), Lewy body diseases (n = 21), and non-neurodegenerative controls (n = 33). Results: CSF TMEM119 levels were elevated in the AD group compared to the control (p = 0.004), CM (p = 0.005), and FTLD (p = 0.023) groups. Levels were higher in both mild cognitive impairment (MCI-AD) and dementia (ADD) subgroups when compared to controls. For the discrimination of AD from controls, the area under the curve (AUC) was 0.78. Discussion: Our results indicate that CSF TMEM119 may have potential as a biomarker representing microglial involvement in early and later stages of AD. Highlights: Elevated levels of TMEM119 were observed in the CSF of patients with AD. Increased CSF TMEM119 was seen in MCI-AD patients compared to controls. Elevated levels in MCI-AD underscore early microglial involvement in AD. In the AD group, an association was found between CSF TMEM119 and CSF total tau. CSF TMEM119 may provide valuable information on neuroinflammation.