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Association of tear fluid glutathione synthetase and glutathione levels with amyloid positivity

ABSTRACT: Tear fluid is a promising source of biomarkers for Alzheimer’s disease (AD). This study characterized the tear fluid proteome across AD and dementia stages. Tear fluid was collected from 60 participants, cognitively normal (CN) individuals (n=32), patients with mild cognitive impairment (n=14), and dementia (n=14). Of these, 27 were amyloid PET-negative and 33 PET-positive. The proteome was analyzed using label-free mass spectrometry, followed by targeted validation immunoassays of key findings. In total, 703 proteins were reliably identified. A notable upregulated protein in dementia compared with CN was glutathione synthetase (GSS) (1.7-fold, p = 0.02). Validation revealed elevated GSS (2-fold) and its product glutathione (1.7-fold) in tear fluid of amyloid PET–positive participants. Incorporating GSS and glutathione as pre-screeners could reduce the need for PET scans by up to 75%. Tear fluid shows promise as a non-invasive source for AD biomarkers, offering novel disease insights, and potential utility for pre-screening prior to PET imaging.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Tear

DISEASE(S): Alzheimer's Disease

SUBMITTER: Ashok Sharma

LAB HEAD: Ashok Sharma

PROVIDER: PXD072063 | Pride | 2026-03-25

REPOSITORIES: Pride

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			Action	DRS
	EMI335.msf	Msf
	EMI335.raw	Raw
	EMI335.xlsx	Xlsx
	EMI360.msf	Msf
	EMI360.raw	Raw

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