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Published on: July 29, 2018

Association of sTREM2 and YKL-40 With Alzheimer's Disease Progression: A Systematic Review

Rasha Omer Babiker Mohamed1, Abubaker M Elamin2, Sara Salim Ali Ahmed3

  • 1Trauma and Orthopedics, Noble's Hospital, Douglas, IMN.

Cureus
|July 25, 2026
PubMed

Insights

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and chitinase-3-like protein 1 (YKL-40) are key Alzheimer's disease biomarkers. Their distinct roles in neuroinflammation and disease progression are clarified, guiding future prognostic research.

Area of Science:

  • Neuroscience
  • Biomarkers
  • Neuroinflammation

Background:

  • Neuroinflammation is central to Alzheimer's disease (AD) pathogenesis.
  • Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and chitinase-3-like protein 1 (YKL-40) are fluid biomarkers reflecting glial reactivity in AD.
  • Their precise roles in AD progression, association with core pathologies, and prognostic value require further elucidation.

Purpose of the Study:

  • To systematically review and synthesize evidence on the associations of sTREM2 and YKL-40 with Alzheimer's disease progression.
  • To clarify the stage-specific roles and prognostic utility of these neuroinflammatory biomarkers.

Main Methods:

  • Systematic review following PRISMA 2020 guidelines, searching major databases (PubMed, MEDLINE, CINAHL, IEEE Xplore, Web of Science) from Jan 2021 to Dec 2025.
  • Inclusion of 13 original human studies measuring sTREM2 and/or YKL-40 across the AD spectrum, with methodological quality assessed using the Newcastle-Ottawa Scale.
  • Narrative synthesis due to heterogeneity in study design and outcomes.

Main Results:

  • Cerebrospinal fluid (CSF) sTREM2 exhibited a biphasic pattern, with early neuroprotective associations and later links to atrophy and cognitive decline, showing a sex-APOE ε4 interaction.
  • YKL-40 demonstrated weak amyloid association but strong coupling with tau pathology and neurodegeneration, influenced by vascular risk factors.
  • Plasma YKL-40 predicted incident dementia and cognitive decline; serum YKL-40 showed good diagnostic performance for early dementia.

Conclusions:

  • sTREM2 and YKL-40 represent distinct yet complementary neuroinflammatory pathways in AD.
  • sTREM2 reflects stage-dependent microglial response, while YKL-40 indicates tau-associated astrocytic activation modulated by vascular factors.
  • Longitudinal studies with concurrent biomarker assessment are crucial for clarifying their combined prognostic value in AD.
Keywords:
alzheimer's diseaseamyloidastrocytecerebrospinal fluid biomarkerschi3l1microglianeuroinflammationstrem2ykl-40

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