Blood Biomarkers to Detect Alzheimer Disease

To the Editor In their excellent research, Dr Palmqvist and colleagues report high diagnostic accuracy of blood biomarkers in the diagnosis of Alzheimer disease. The authors used the STROBE checklist for observational studies, but this is a prospective diagnostic accuracy study, for which the STARD checklist is more appropriate.

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Febbraio 2025

Abstract TP393: Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer’s Models

Stroke, Volume 56, Issue Suppl_1, Page ATP393-ATP393, February 1, 2025. Dysregulation of the immune system is a contributing factor in the progression of Alzheimer’s Disease (AD), likely by increased vascular inflammation triggered by brain or peripheral inflammation. Our research has demonstrated that neutrophils play a role in causing hypoperfusion by adhering to and obstructing blood vessels, as seen in both mouse models for and patients with AD. Notably, protein glycosylation of membrane proteins is essential for regulating the adhesion properties of neutrophils to immune cells and the vasculature.Here, we utilize lectin blots to show that sialic acid residues, which are the terminal caps of glycosylation chains, are increased on neutrophil membrane proteins from an amyloidosis Alzheimer’s mouse model. Furthermore, we evaluated the efficacy of the sialyltransferase inhibitor alpha 2,3 sialyltransferase-IN-1 by lectin blot analyses, identifying it to be an effective compound for removing sialic acid from neutrophil membrane proteins. Notably, we performedin vivomultiphoton imaging of cerebral blood flow and capillary stalling in AD mice injected with alpha 2,3 sialyltransferase-IN-1. Our findings demonstrated that reducing sialic acid residues on neutrophils improved cerebral blood flow and capillary stalling.This work suggests that the altered glycosylation pattern, specifically aberrant sialylation residues of neutrophil glycoproteins, are a significant contributing factor to the hypoperfusion observed in AD mouse models and patients. Modulating the glycosylation profile may present a potential therapeutic approach for improving the vascular dysfunction associated with AD pathogenesis.

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Gennaio 2025