Related Experiment Video
Updated: May 12, 2026
06:52
Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease
Published on: July 6, 2019
Defective regulated secretion: A trigger for Alzheimer's pathology?
Bhavna Verma1, Preman Singh2, Deborah C I Goberdhan3
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Progress in Neurobiology
|May 10, 2026
Summary
Alzheimer's Disease (AD) neurodegeneration may stem from intraneuronal endolysosome defects, potentially triggered by Amyloid-β (Aβ) accumulation during regulated secretion. Targeting these early intracellular pathways offers novel therapeutic strategies for AD.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Alzheimer's Disease (AD) is characterized by amyloid plaques and neurofibrillary tangles.
- Intraneuronal endolysosome defects are increasingly implicated as an early trigger for AD neurodegeneration.
- These defects may be induced by Amyloid-β (Aβ) and tau pathologies.
Purpose of the Study:
- To investigate the role of regulated secretion in initiating intraneuronal endolysosome defects in AD.
- To explore novel intracellular mechanisms driving neurodegeneration in early AD.
- To identify potential therapeutic targets for early AD intervention.
Main Methods:
- Analysis of intracellular trafficking in neuronal and non-neuronal cells using high-resolution techniques.
- Investigating the interplay between Amyloid Precursor Protein (APP), secretases, and endolysosomal compartments.
- Examining the impact of Aβ accumulation and C-terminal fragments on endolysosomal function.
Main Results:
- Aberrant compartmental maturation during regulated secretion leads to endolysosome defects.
- APP, secretases, and endosomal compartments converge during these aberrant events.
- Aβ accumulation interferes with endolysosomal trafficking and may induce tau pathology.
- Secreted proteins from Aβ-laden compartments can induce endolysosomal phenotypes in other cells.
Conclusions:
- Regulated secretion plays a critical role in the initiation of AD pathology via intraneuronal endolysosome dysfunction.
- Novel intracellular pathways driving neurodegeneration are highlighted.
- Identifying suppressors of these pathways could lead to new early-stage AD therapies.
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