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Live-imaging in neurons to study Alzheimer's disease

The regulation of the Alzheimer's disease-related protein BACE1 transport in neurons
by

Virginie Buggia-Prevot

on 26 June 2014

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Transcript of Live-imaging in neurons to study Alzheimer's disease

Role of EHD proteins in Alzheimer's disease

Visualization of BACE1 trafficking after internalization
BACE1 transport in dendrites
BACE1 bidirectional transport in axons
Development of internalized BACE1 Assay
EHD1 and EHD3 as novel regulators of BACE1 trafficking
Unidirectional dendritic transport of internalized BACE1
Internalized BACE1 localization in neurons
Internalized BACE1 localizes in neuronal endosomes
Why BACE1 moves in one direction despite the microtubules mixed polarity in dendrites?!
The regulation of slow endocytic recycling
Virginie Buggia-Prevot , Ph.D.
Role of endosomal transport in Alzheimer's disease
Acknowledgements
Prof. Gopal Thinakaran Lab
Prof. Robert Vassar
Prof. Lawrence Rajendran
UoC Imaging Core Facility
Celia G. Fernandez
Dr. Kulandaivelu Vetrivel
Jelita Roseman
Dr. Xavier Meckler
Aureliane Elie

Prof. Hamid Band
Dr. Vytas Bindokas
Dr. Manju George
Dr. Vinod Udayar
Retrograde dendritic transport of internalized BACE1 require EHD1 and EHD3 activity
EHDs are required for BACE1 dynamics in axons
secretory vesicles dynamics is normal
EHDs are required for axonal localization of BACE1
EHDs colocalize with BACE1 and in APP CTFs in mouse hippocampal mossy fibers
EHD1

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BACE1
EHD1

EHD1

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APP CTFs
DG
MF
CA3
70% of Abeta released in the brain requires endocytosis
Alzheimer's
disease
Genome Wide-Association Study highlighted endosomal genes in AD
Enlarged endosomes in AD brains
Healthy
Brain
Rab5
Abeta
Cataldo et al. 2004
Bertram et al., Nature Genetics, 2007
70% of Abeta production requires endocytosis
Amyloid deposits
Abeta production
in endosomes
Regulation of BACE1 transport and Abeta production by EHDs

siRNA knockdown of EHD expression lowers Abeta in neurons
Vinod Udayar - Rajendran's lab
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Society for Neuroscience Nanosymposium - November 2013
Molecular Motor
Microtubule
Mutants EHDs don't change Internalized BACE1
distribution in endosomes
Check out the publication in Cell Reports:
http://www.cell.com/cell-reports/fulltext/S2211-1247%2813%2900736-5
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