Pyroptosis executive protein GSDMD as a biomarker for diagnosis and identification of Alzheimer’s disease

Abstract

Objective: This study was mainly conducted to explore the expression changes of GSDMD and conventional markers (including T-Tau, Tau181p, and Aβ1–42) in the cerebrospinal fluid among patients with Alzheimer's disease (AD) and vascular dementia (VD), followed by determination of role of GSDMD in diagnosing and identifying AD and VD. Methods: In this study, 60 patients with VD, 60 patients with AD, and 50 healthy controls were enrolled. Lumbar puncture was performed to collect cerebrospinal fluid samples. Patients with VD and patients with AD were evaluated using the Mini-Mental State Examination (MMSE) scale, Montreal Cognitive Assessment (MoCA) scale, Clinical Dementia Rating (CDR) scale, Activity of Daily Living (ADL) scale, and Neuropsychiatric Inventory (NPI) questionnaire, aiming to determine the behavioral ability of patients. ELISA kit was purchased to determine the levels of GSDMD, T-Tau, Tau181p, and Aβ1–42 in cerebrospinal fluid, and the expression of inflammatory factors, IL-1β and IL-6, was also detected. Results: (1) The levels of GSDMD, T-Tau, and Tau181p in the cerebrospinal fluid were higher in patients with AD than those of patients with VD and healthy controls, while the levels of Aβ1-42 in the cerebrospinal fluid were lower in patients with AD than that in healthy controls and patients with VD. (2) GSDMD had good diagnostic accuracy in AD. Additionally, GSDMD, T-Tau, Tau181p, and Aβ1-42 had good discrimination accuracy in distinguishing AD and VD. (3) The expression levels of inflammatory factors (IL-1β and IL-6) in cerebrospinal fluid were higher in patients with AD than those of healthy controls and patients with VD, which were positively correlated with GSDMD expression. Conclusion: The expression of GSDMD was increased in patients with AD, which could be used as a biomarker for AD diagnosis and identification from VD.