# 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

## TL;DR

The study found higher levels of TMEM119 in cerebrospinal fluid of Alzheimer's patients, suggesting microglial involvement even in early stages.

## Contribution

This is the first study to show that TMEM119 could serve as a biomarker for microglial activity in Alzheimer's disease.

## Key findings

- CSF TMEM119 levels were elevated in Alzheimer's disease compared to controls, CM, and FTLD.
- Increased TMEM119 was observed in mild cognitive impairment due to Alzheimer's.
- TMEM119 levels correlated with total tau in Alzheimer's patients.

## Abstract

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.

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).

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.

Our results indicate that CSF TMEM119 may have potential as a biomarker representing microglial involvement in early and later stages of AD.

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.

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.