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Basic Science and Pathogenesis.

Xiaoli Hao1, Xuewen Xiao1, Ling Weng1

  • 1Xiangya Hospital, Central South University, Changsha, Hunan, China.

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|December 23, 2025
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Summary
This summary is machine-generated.

Genetic factors like APOE ε4 and USP13 variants increase dementia with Lewy bodies (DLB) risk in East Asians. Polygenic risk scores and plasma biomarkers show diagnostic potential for DLB.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biomarkers

Background:

  • Limited genetic research exists for dementia with Lewy bodies (DLB) in East Asian populations.
  • Understanding genetic risk factors and plasma biomarkers is crucial for DLB diagnosis and management.

Purpose of the Study:

  • To conduct the first genetic investigation of DLB in East Asia.
  • To identify genetic associations with DLB risk and explore the utility of plasma biomarkers for diagnosis.

Main Methods:

  • Whole genome sequencing was performed on 151 DLB patients and 2010 controls.
  • Plasma levels of GFAP, αSyn, NfL, and p-tau217 were measured in a subgroup.
  • Associations were validated using the ChinaMAP database.

Main Results:

  • The APOE ε4 allele and a rare USP13 gene variant were significantly associated with increased DLB risk.
  • DLB patients exhibited higher plasma levels of GFAP, αSyn, NfL, and p-tau217.
  • Polygenic risk scores (PRS) combined with plasma biomarkers achieved an AUC of 0.927 for DLB diagnosis.

Conclusions:

  • This study provides the first genetic insights into DLB in East Asia.
  • APOE ε4 and USP13 variants are significant risk factors for DLB.
  • PRS and plasma biomarker assays demonstrate strong potential for DLB diagnosis.