Evidence map›Paper›PMID 42903321›Full record

ArticleFrontiers in aging neuroscience2026

Reduced serum LEFTY2 and disease-dependent biomarker associations in Alzheimer's disease: an exploratory study.

Wei Wuli, Raymond Y Lo, Horng-Jyh Harn, Tzyy-Wen Chiou, Yue-Xuan Xu, Yuncin Luo, Ivan Wijaya, Shinn-Zong Lin

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Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Wei Wuli *Bioinnovation Center, Hualien Tzu Chi Hospital, Hualien, Taiwan.
Raymond Y Lo *Center for Dementia Care, St. Mary's Hospital, Taitung, Taiwan.
Horng-Jyh HarnBioinnovation Center, Hualien Tzu Chi Hospital, Hualien, Taiwan.
Tzyy-Wen ChiouDepartment of Biochemistry and Molecular Medicine, National Dong Hwa University, Hualien, Taiwan.
Yue-Xuan XuBioinnovation Center, Hualien Tzu Chi Hospital, Hualien, Taiwan.
Yuncin LuoDepartment of Neurology, Hualien Tzu Chi Hospital, Hualien, Taiwan.
Ivan WijayaBioinnovation Center, Hualien Tzu Chi Hospital, Hualien, Taiwan.
Shinn-Zong LinBioinnovation Center, Hualien Tzu Chi Hospital, Hualien, Taiwan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reliable blood-based biomarkers are increasingly needed for the detection and monitoring of Alzheimer's disease (AD). Left-right determination factor 2 (LEFTY2) is a secreted protein of the transforming growth factor-β (TGF-β) superfamily. Evidence from AD-related neuronal models suggests that LEFTY2 promotes neuronal survival, attenuates amyloid- and tau-related pathology, and suppresses inflammatory responses, highlighting its potential relevance to AD. However, its clinical significance and relationship with AD-related blood biomarkers remain unclear. In this study, we investigated the association between serum LEFTY2 and and biomarkers associated with amyloid pathology, tau pathology, neuroinflammation, and neurodegeneration in patients with AD and age-matched cognitively normal (CN) controls. Biomarker levels were quantified using enzyme-linked immunosorbent assays. Serum LEFTY2 levels were significantly lower in AD patients than in cognitively normal controls, whereas Amyloid-beta 1-40 (Aβ1-40), phosphorylated tau (pTau) 181 and Neurofilament light chain (NF-L) levels were significantly elevated. Correlation analyses revealed a positive association between LEFTY2 and Aβ1-42 in AD patients, while correlations with biomarkers of tau pathology, inflammation, and neurodegeneration were less consistent. In cognitively normal controls, LEFTY2 was negatively correlated with total tau and positively correlated with TGF-β1. Collectively, these findings indicate that LEFTY2 exhibits distinct associations with AD-related biomarkers in a disease-dependent manner. These exploratory findings provide new insights into the relationships among circulating AD biomarkers and support further investigation of LEFTY2 as a novel candidate blood-based marker in larger prospective cohorts.

Indexed as

Alzheimer’s diseaseAβ1-42blood-based biomarkersLEFTY2pTau181TGF-β1

Identifiers

PMID42903321
PMCPMC13680440

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.