Amyloidosis: Diagnosis, Treatment, Outcomes

Mathematical Modeling of AA Amyloidosis: Coupling SAA-HDL Binding Dynamics with Path-Dependent Renal Aging

This paper develops a mathematical model linking SAA-HDL binding dynamics to renal amyloidosis progression, showing how inflammation patterns and SAA levels affect disease outcomes.

Computational alternative to cardiac biopsy in multiple myeloma: utilizing the shape of routine laboratory data for the classification of AL cardiac amyloidosis

The paper develops machine learning models to classify AL cardiac amyloidosis in multiple myeloma patients using electronic medical records instead of cardiac biopsy.

Modulating Transthyretin Fibril Stability with D-Retro-Inverso Peptides

The paper uses molecular dynamics simulations to study how D-Retro-Inverso peptides modulate TTR fibril stability and identifies DRI-K6V as a potential disruptor of TTR fibrils.

Reply to: Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy

The paper investigates structural polymorphism in ATTR amyloid fibrils from a fourth patient, extending previous findings of two cardiac polymorphs to other organs.

Early Steps in Pathogen-induced TTR-amyloid-formation

The paper uses molecular dynamics simulations to investigate if SARS-CoV-2 peptides can initiate TTR tetramer dissociation, leading to amyloidosis.

Targeting Sec61 to Silence Pathogenic Light-Chain Production in AL Amyloidosis

This study targets the Sec61 translocon to suppress pathogenic light-chain production in AL amyloidosis, showing that mycolactone and synthetic inhibitors like A317 reduce LC secretion while highlighting the need for client selectivity.

An N-terminal ATTR Fibril Segment Promotes Transthyretin Amyloid Nucleation and Polymorphism

This study identifies an N-terminal ATTR fibril segment that promotes TTR amyloid nucleation and polymorphism through structural compatibility and templating activity.

FibrilNet maps conserved and tissue-specific molecular environments across systemic amyloidoses

The paper introduces FibrilNet, a network framework that identifies conserved and tissue-specific molecular environments across systemic amyloidoses by integrating proteomic data with semantic and interaction information.

Cryo-EM reveals patient- versus organ-specific structural diversity and bound ligands in lambda-6 light chain amyloids

The paper uses cryo-EM to analyze lambda-6 light chain amyloid structures from different organs and patients, revealing structural diversity and potential interactions with collagen-VI.

Does Human Transthyretin Aggregate in Blood Plasma or in Cardiac Tissue? A Mathematical Modeling Study

This study uses a mathematical model to show that TTR aggregation primarily occurs in cardiac tissue, not blood plasma, and predicts fibril accumulation linked to disease progression and mortality.

Polymorphic IGLV6-57 AL amyloid fibrils and features of a shared folding pathway

The paper reports cryo-EM structures of cardiac AL amyloid fibrils from IGLV6 light chains, revealing conserved structural motifs and sequence-dependent folding mechanisms.

Hybrid Tetramers of Wild-Type and Amyloidogenic H88R Transthyretin Challenge the Monomer Paradigm

This study shows that H88R transthyretin can form hybrid tetramers with wild-type chains, challenging the monomer paradigm in ATTRv.

From Hummingbird to Elephant: Amyloid Formation in Natural Transthyretin Variants

This study compares the aggregation behavior of TTR variants from hummingbirds and elephants under mechanical agitation, revealing differences linked to their physiological adaptations.

Small molecule stabilization of diverse amyloidogenic immunoglobulin light chains revealed by hydrogen-deuterium exchange mass spectrometry

This study identifies small molecules that stabilize diverse amyloidogenic immunoglobulin light chains by reducing conformational dynamics and proteolysis.

Exploring light chain cardiotoxicity in AL amyloidosis: Impact on hiPSC-derived Cardiomyocyte Activity

This study uses hiPSC-derived cardiomyocytes to show that cardiotoxic light chains reduce electrophysiological function, while non-toxic light chains have no effect.

Proteomic profiling of whole tissue sections in cardiac ATTR amyloidosis reveals increased extracellular matrix remodeling

The paper uses proteomics to show increased ECM remodeling and complement activation in cardiac ATTR amyloidosis.

Extracellular chaperones modulate AL light chains fibrillar aggregation and contribute to amyloid structural heterogeneity

This study shows that extracellular chaperones like apoE3 and CLU modulate amyloid light chain aggregation and fibril structure, affecting disease pathophysiology and structural variability.

Transthyretin amyloid fibrils adopt distinct folds in the brain

This study determines cryo-EM structures of brain-derived ATTR fibrils from patients with V30M and V30G variants, revealing distinct folds compared to peripheral tissues.

Early plasma proteomic alterations precede amyloidosis diagnosis, reflecting cardiac and immune dysregulation

The paper identifies early plasma proteomic changes preceding amyloidosis diagnosis, showing cardiac and immune dysregulation before clinical symptoms.

Structural polymorphism of ex-vivo ALECT2 amyloid fibrils revealed by cryo-EM

This study uses cryo-EM to reveal structural polymorphism in ex-vivo ALECT2 amyloid fibrils, identifying three morphologies and acetylation sites.

Preventing pathogenic dimerization in a misfolded antibody light chain through the design of an inhibitory peptide

This study designs an inhibitory peptide to prevent pathogenic dimerization of a misfolded antibody light chain by optimizing its sequence to maximize interface complementarity.

AUTOTAC-mediated targeted degradation of transthyretin aggregates ameliorates hereditary transthyretin amyloidosis

This study identifies the N-degron pathway's role in lysosomal degradation of TTRV30M aggregates and demonstrates the therapeutic potential of AUTOTAC-based degraders for hATTR.

Tracing the origin of Finnish gelsolin amyloidosis using haplotype sharing trees

This study traces the geographic origin of a Finnish founder variant causing gelsolin amyloidosis using haplotype sharing trees and estimates its most recent common ancestor.

3D Visualization and Proteomic Analysis of Human Cardiac Transthyretin Amyloidosis Tissue Reveals Microangiopathy and Capillary Occlusion

This study uses proteomics and 3D imaging to show that ATTR cardiac amyloidosis involves microangiopathy, capillary occlusion, and vascular basement membrane congestion.

Phenomenological model of transthyretin stabilization

This study investigates why TTR levels rise after treatment with stabilizers by proposing mechanisms beyond reduced dissociation.

Preclinical characterization of AT-03, a novel Serum Amyloid P fusion protein that demonstrates pan-amyloid binding and removal

This paper characterizes AT-03, a novel fusion protein that binds and removes various amyloid types, showing therapeutic efficacy in a mouse model.

Accelerated Apolipoprotein A-II senile amyloidosis in a PAI-1 (plasminogen activator inhibitor 1) knock-out model

This study shows PAI-1 knockout mice develop systemic AApoA-II amyloidosis at intermediate age, with amyloid deposits in multiple organs and urinary albumin as a biomarker, highlighting potential risks of PAI-1 inhibition in amyloidosis.

Intracellular aggregation of the transthyretin protein is limited by Hsp70 chaperones

This study shows that Hsp70 chaperones limit intracellular TTR aggregation in yeast, suggesting their decline may contribute to age-related TTR amyloidosis.

Structure of ATTRv-F64S fibrils isolated from skin tissue of a living patient

The paper reports the first cryo-EM structure of ATTRv-F64S fibrils from a living patient's skin tissue, validating skin biopsy as a non-invasive diagnostic tool.

Mathematical Modeling of Late-Stage LC Aggregation and Cardiac Injury Following Establishment of a Pathogenic Plasma-Cell Clone

This study develops a mathematical model to simulate LC aggregation and cardiac injury in AL amyloidosis, showing that cardiac tissue aggregation leads to greater fibril deposition and cardiotoxicity than plasma aggregation.