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

Sep 28, 2026

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Evaluate transmembrane protein 119 (TMEM119) in cerebrospinal fluid (CSF) as a differential diagnostic biomarker for neurodegenerative diseases. After assay validation, enzyme-linked immunosorbent assay quantified CSF TMEM119 in 174 patients across Alzheimer’s disease, amyotrophic lateral sclerosis, cerebral microangiopathy, frontotemporal lobar degeneration, Lewy body diseases, and controls. CSF TMEM119 increased in Alzheimer’s disease versus controls and in MCI-AD and dementia subgroups; AUC for AD discrimination reached 0.78. Results support TMEM119 as a marker of microglial involvement in early and later Alzheimer’s stages.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Methods

Results

Discussion

Background

Alzheimer’s disease and neuroinflammation

Microglia and TMEM119

DOI: 10.1002/dad2.70240 RESEARCH ARTICLE 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 Paula Klassen1 ChristoforosAlexudis2 Veronika Klose1 NereaGómez de San José2 André Huss2 Franziska Bachhuber2 Önder Soylu2 Badrieh Fazeli2 Deborah Erhart2 Mona Laible2 Sarah Anderl-Straub2 Sarah Jesse2 Markus Otto3 Albert C. Ludolph2 Hayrettin Tumani2 Steffen Halbgebauer2 1 German Center for Neurodegenerative Diseases (DZNE e.V.), Ulm, Germany 2 Department of Neurology, Ulm University Hospital, Ulm, Germany 3 Department of Neurology, University Hospital Halle, Halle (Saale), Germany Correspondence Hayrettin Tumani, Department of Neurology, Ulm University Hospital, Oberer Eselsberg 45, Ulm, 89081, Germany. Email: [hayrettin.tumani@uni-ulm.de](hayrettin.tumani@uni-ulm.de) Funding information German Center for Neurodegenerative Diseases; Ulm University, and Chemische Fabrik Karl Bucher GmbH; German Federal Ministry of Education and Research, Grant/Award Number: 01GI1007A; EU Joint Programme-Neurodegenerative Disease Networks Genfi-Prox; EU (MOODMARKER, PREDICT-FTD); German Research Foundation/DFG, Grant/Award Number: SFB1279; Baden-Württemberg, Grant/Award Number: D.3830; Boehringer Ingelheim Ulm University BioCenter, Grant/Award Number: D.5009; Thierry Latran Foundation 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: CSFTMEM119 levels were elevated intheAD 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 CSFTMEM119 may have potential as a biomarker representing microglial involvement in early and later stages of AD. KEYWORDS Alzheimer’s disease, biomarkers, cerebrospinal fluid, microglia, neuroinflammation Highlights ∙ Elevated levels ofTMEM119 were observed in the CSF of patients with AD. ∙ Increased CSFTMEM119 was seen in MCI-AD patients compared to controls. ∙ Elevated levels in MCI-AD underscore early microglial involvement in AD. Hayrettin Tumani and Steffen Halbgebauer contributed equally to this study and share senior authorship. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Author(s). Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2026;18:e70240. [https://doi.org/10.1002/dad2.70240](https://doi.org/10.1002/dad2.70240) wi[leyonlinelibrary.com/journal/dad2](leyonlinelibrary.com/journal/dad2) 1of10 ∙ In the AD group, an association was found between CSF TMEM119 and CSF total tau. ∙ CSFTMEM119 may provide valuable information on neuroinflammation. 1 BACKGROUND Alzheimer’s disease (AD) is recognized as the most common cause of dementia.1 It is characterized by memory impairment and progressive cognitive decline and has been shown to have a preclinical phase that can last several decades.2,3 Major pathol

FAQs

What is the study evaluating as a potential diagnostic biomarker?

The study evaluates transmembrane protein 119 (TMEM119) levels in cerebrospinal fluid as a (differential) diagnostic biomarker for neurodegenerative diseases.

How were CSF TMEM119 levels measured and in which patient groups?

After assay validation, CSF TMEM119 was measured using an enzyme-linked immunosorbent assay in 174 patients across six diagnostic groups, including Alzheimer’s disease, ALS, cerebral microangiopathy, FTLD, Lewy body diseases, and non-neurodegenerative controls.

What were the main findings regarding TMEM119 levels in Alzheimer’s disease?

CSF TMEM119 levels were elevated in the Alzheimer’s disease group compared with controls and other disease groups, and levels were higher in the MCI-AD and dementia subgroups. Discrimination of Alzheimer’s disease from controls yielded an AUC of 0.78.

Sep 28, 2026

Uploaded by Levi