Related Experiment Video
Updated: May 21, 2026

Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease
Published on: July 6, 2019
Multi-compartmental modeling of SORLA's influence on amyloidogenic processing in Alzheimer's disease
Angelyn Lao1, Vanessa Schmidt, Yvonne Schmitz
1Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, Germany.
Background:
Proteolytic breakdown of the amyloid precursor protein (APP) by secretases is a complex cellular process that results in formation of neurotoxic Aβ peptides, causative of neurodegeneration in Alzheimer's disease (AD). Processing involves monomeric and dimeric forms of APP that traffic through distinct cellular compartments where the various secretases reside. Amyloidogenic processing is also influenced by modifiers such as sorting receptor-related protein (SORLA), an inhibitor of APP breakdown and major AD risk factor.
Results:
In this study, we developed a multi-compartment model to simulate the complexity of APP processing in neurons and to accurately describe the effects of SORLA on these processes. Based on dose-response data, our study concludes that SORLA specifically impairs processing of APP dimers, the preferred secretase substrate. In addition, SORLA alters the dynamic behavior of β-secretase, the enzyme responsible for the initial step in the amyloidogenic processing cascade.
Conclusions:
Our multi-compartment model represents a major conceptual advance over single-compartment models previously used to simulate APP processing; and it identified APP dimers and β-secretase as the two distinct targets of the inhibitory action of SORLA in Alzheimer's disease.
Related Concept Videos
Alzheimer Disease ll: Pathophysiology
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease l: Introduction

