Kristine K. Freude (Denmark)
University of Copenhagen
Department of Veterinary and Animal Sciences
Associate Professor Kristine Freude is currently employed by the Health and Science Department at the University of Copenhagen and Director of the Centre of Excellence in Neuroscience "BrainStem". She received her PhD in 2005 from the Free University and Max-Planck Institute for Molecular Genetics in Berlin, Germany investigating genes involved in neuronal development and mental retardation. She continued her postdoctoral training at the University at Irvine, California USA from 2005 until 2011. Here she first worked on pancreas development, followed by exploring and establishing stem cell models for Alzheimer's disease in Prof. Frank LaFerla's group. Her research was sponsored by the California Institute for Regenerative Medicine. Since 2012 Kristine is implementing her research within neurodegenerative diseases at the University of Copenhagen.

Presenter of 1 Presentation

 Conference Calendar

IMPLICATIONS OF GOLGI FRAGMENTATION IN HIPSC DERIVED NEURONS

Session Name
0640 - SINGLE-CELL GENOMICS STEM CELLS 3 (ID 34)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 113
Lecture Time
09:10 AM - 09:25 AM
Presenter

Abstract

Aims

Alzheimer’s disease (AD) is the most common cause of dementia, with no current cure. Familial AD (fAD) can be caused by mutations in APP or PSEN1 and PSEN2. Our human induced pluripotent stem cell (hiPSC) model consists of patient hiPSC with mutations in PSEN1 (A79V and P150L) and their respective isogenic controls generated via CRISPR-Cas9 precision gene editing.

Methods

The respective hiPSC have been differentiated into cortical glutamatergic neurons and displayed disease characteristic phenotypes such as increased Abeta secretion, Tau hyperphosphorylation and mitochondrial and synaptic deficits. Intriguingly, these neurons displayed Golgi fragmentation, indicating impairments in protein processing and post-translational modifications. RNA sequencing showed differentially expressed genes involved in glycosylation and glycan patterns.

Results

Such processes take mainly place in the Golgi apparatus, linking Golgi fragmentation and impaired processing. These results were further supported by lectin assays as well as glycan profiling. Golgi fragmentation appears to be an early event in AD pathogenesis, observed prior to mitochondrial and synaptic dysfunctions. Additionally, Golgi fragmentation could be induced in control neurons via Abeta treatment, suggesting a potential cascade of Abeta accumulation, triggering Golgi fragmentation, causing impaired processing of key proteins and metabolites, resulting in neurodegeneration.

Conclusions

Our research highlights the potential of iPSC disease modelling, as well as Golgi processing and glycosylation as possible entry points for AD intervention.

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