Published: 31-01-2023 16:01 | Updated: 01-02-2023 16:04

New thesis on subcellular Aβ mechanisms and treatment strategies in Alzheimer Disease

Hi Yang Gao, PhD student at the Division of Neurogeriatrics. On February 24 you will defend your thesis "Alzheimer Disease: Subcellular Aβ mechanisms and treatment strategies", what is the main focus of the thesis?

Yang Gao, PhD student at the Division of Neurogeriatrics, NVS. Photo: Private.

This thesis focuses on the amyloid β-peptide (Aβ) induced toxicity and mechanisms in hippocampal neurons at the subcellular level and explores effective treatment strategies for Alzheimer disease (AD). Aβ is the key molecule in the pathogenesis of AD, but the mechanisms of its toxicity are still largely unknown.

Which are the most important results?

We found that Aβ42 could oligomerizes in neurons in a concentration-dependent manner. Especially, internalized Aβ42 oligomerizes with higher efficiency than Aβ40 because of its enhanced uptake and tendency to aggregation.  Moreover, we found that internalized Aβ42 accumulates with time in neurons and causes endolysosomal leakage when the intravesicular Aβ42 concentration reaches a high level. Aβ42-induced endolysosomal leakage and AEP release could be a potential mechanism underlying tau hyperphosphorylation.

How can this new knowledge contribute to the improvement of people's health?

The findings in this thesis increase the understanding of the role of intracellular Aβ in AD and add details to the amyloid cascade hypothesis. Moreover, studies on Bri2 BRICHOS in this thesis also support it as a potential anti-amyloid treatment strategy.

What's in the future for you? Will you keep on conducting research?

I would like to continue studies on Aβ mechanisms in AD, and I’m also interested in looking for new biomarkers for AD.


Yang Gao Phd Student