Mechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants - Scorecard - MDSpire

Mechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants

  • By

  • Nurun N. Fancy

  • Nanet Willumsen

  • Vicky M. N. Chau

  • Samuel L. Boulger

  • Harry J. Whitwell

  • Wenhao Wang

  • Baptiste Avot

  • Michael Thomas

  • Jonathan Talbot-Martin

  • Stergios Tsartsalis

  • Combiz Khozoie

  • Aisling McGarry

  • Eleonore Schneegans

  • Riad Yagoubi

  • To Ka Dorcas Cheung

  • Marianna Papageorgopoulou

  • Emily Adair

  • Benjamin Cooper

  • Karen Davey

  • Amy M. Smith

  • William Scotton

  • John Hardy

  • Paul M. Matthews

  • Johanna S. Jackson

  • June 15, 2026

  • 0 min

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Clinical Scorecard: Pathological Mechanisms of Alzheimer’s Disease Associated with TREM2 Variants R47H and R62H

At a Glance

CategoryDetail
Condition
Key MechanismsTREM2 variants R47H and R62H affect microglial function, β-amyloid clearance, and neuronal loss, leading to increased AD risk.
Target Population
Care Setting

Key Highlights

  • TREM2 coding variants increase genetic risk for late-onset AD.
  • R47H variant confers the highest relative AD risk (~3.9 times that of common variants).
  • R62H variant has a smaller effect on disease risk (~1.4 times common variants).
  • TREM2 KO models show reduced β-amyloid clearance and increased neuritic plaque density.
  • Distinct astrocytic and neuronal response signatures are associated with TREM2 variants.

Guideline-Based Recommendations

Diagnosis

    Management

    • Consideration of TREM2 variant status in the context of AD pathology, including potential clinical trials or targeted therapies.

    Monitoring & Follow-up

      Risks

        Patient & Prescribing Data

        Patients with identified TREM2 variants and clinical signs of AD.

        Current treatments may need to be tailored based on TREM2 variant status.

        Clinical Best Practices

        • Utilize immunohistochemistry and imaging mass cytometry for characterizing AD pathology.
        • Conduct single nuclear RNA sequencing for differential gene expression analysis.
        • Incorporate genetic risk factors into patient management strategies.

        Related Resources & Content

        Original Source(s)

        Mechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants

        • by Nurun N. Fancy, Nanet Willumsen, Vicky M. N. Chau, Samuel L. Boulger, Harry J. Whitwell, Wenhao Wang, Baptiste Avot, Michael Thomas, Jonathan Talbot-Martin, Stergios Tsartsalis, Combiz Khozoie, Aisling McGarry, Eleonore Schneegans, Riad Yagoubi, To Ka Dorcas Cheung, Marianna Papageorgopoulou, Emily Adair, Benjamin Cooper, Karen Davey, Amy M. Smith, William Scotton, John Hardy, Paul M. Matthews, Johanna S. Jackson

        • June 15, 2026

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