# Exploring the Histopathological Features of Thrombus-Associated Localized Amyloid Deposition: Comprehensive Analysis Employing Immunohistochemistry and Proteomics

## TL;DR

This study investigates amyloid deposits in blood clots and identifies key proteins involved, offering insights into how these deposits form and are cleared.

## Contribution

The study identifies apolipoprotein A-I, transthyretin, and lactoferrin as key components of amyloid deposits in thrombi and suggests a cross-seeding mechanism for their formation.

## Key findings

- Amyloid deposits in thrombi and vessel walls mainly consist of apolipoprotein A-I, transthyretin, and lactoferrin.
- Phagocytes primarily clear amyloid deposits from vessel walls rather than within the thrombus itself.
- Amyloid deposits may migrate from the thrombus to the vessel wall during thrombus processing.

## Abstract

Amyloid deposition has been reported to localize within thrombi; however, its pathological characteristics, particularly its precursor proteins, remain poorly understood. This study aimed to elucidate the pathological features of thrombus-associated amyloid deposition by immunohistochemistry combined with proteomic analyses using liquid chromatography–tandem mass spectrometry with laser microdissection. Our findings revealed that thrombus-associated amyloid deposits within the thrombus and vessel wall primarily comprised apolipoprotein A-I, with a mixture of amyloid fibrils derived from amyloidogenic proteins, including transthyretin and lactoferrin. Given that these proteins are present in the blood, our results support a previous hypothesis that proteins denatured during thrombus aging are a source of amyloid. Furthermore, phagocytes were infiltrated around the intramural and extravascular deposits rather than around the amyloid deposits within the thrombus. Therefore, amyloid deposits generated within the thrombus may be transported from regions with limited blood flow to the vessel wall and surrounding tissues, where blood flow is present, during thrombus processing. These deposits were primarily removed by phagocytic cells. Our results suggest that a facilitative effect on deposition occurs via a cross-seeding mechanism between amyloid fibrils and that phagocytes can remove amyloid deposits. These findings help elucidate the pathogenesis of localized amyloidosis.