Selective vulnerability to neurodegeneration

Research page Walker Jackson

Neurodegenerative diseases cause stereotypical signs based on the specific brain region that is targeted. We try to understand how unaffected regions resist disease with the hope that these secrets can be transferred to vulnerable brain regions.

Our lab addresses the question of why neurodegenerative diseases target specific brain regions, at least initially, a feature known as selective vulnerability. For example, brain regions important for motor control are severely damaged in Huntington’s disease, while brain regions important for memory are severely damaged in Alzheimer’s disease.

Genetic neurodegenerative diseases are especially enigmatic because all cells carry the disease inducing mutation and yet most resist the disease. Moreover, these mutations are expressed for decades before disease sets in. How does the brain resist the toxic protein for so long and why does it eventually fail?

We have two basic questions regarding selective vulnerability:

1) Does a given brain cell respond differently to different protein misfolding stressors and

2) Do different cell types respond to the same stressor differently?

We hypothesize that the effectiveness of the protein quality control machinery differs between different cell types due to different compilations of machinery components and clients and these differences strongly influence selective vulnerability. 

To study the phenotypes of specific cell types in the brain prior to disease onset, we have employed a technique that enables the isolation of mRNAs from the cells of interest. This is accomplished by expressing in specific cell types a modified ribosome protein (called RiboTag) that carries a molecular handle which we use to capture translating ribosomes and determine which proteins the cells are attempting to make. 

Our work with RiboTag revealed that cells that are thought to resist disease show dramatic changes early, while cells that are severely affected late in disease show no response early. These surprising results inspired us to create a new technique that enables us to study multiple layers of gene regulation, from chromatin modulation to translation, all from specific cell types of complex tissues.  


Walker Jackson fov

Research group


Open positions

We are happy to receive applications from people interested in our work, who would like to perform an internship or a master thesis project in the lab.

We especially encourage students interested in pursuing a bioinformatic project involving R programming and/or building online shiny applications for visualizing scientific data. Minimum basic knowledge of R is required.

Please e-mail Lech Kaczmarczyk or Walker Jackson to discuss the possibilities.


Publications from DiVA




Jill R. Crittenden, Shenyu Zhai, Magdalena Sauvage, Takashi Kitsukawa, Eric Burguiere, Morgane Thomsen, Hui Zhang, Cinzia Costa, Giuseppina Martella, Veronica Ghiglieri, Barbara Picconi, Karen A. Pescatore, Ellen M. Unterwald, Walker Jackson, David E. Housman, S. Barak Caine, David Sulzer, Paolo Calabresi, Anne C. Smith, D. James Surmeier, Ann M. Graybiel (2021) CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors Neurobiology of Disease, Vol. 158 Continue to DOI




Kan Xie, Devon P. Ryan, Brandon L. Pearson, Kristin S. Henzel, Frauke Neff, Ramon O. Vidal, Magali Hennion, Isabelle Lehmann, Melvin Schleif, Susanne Schröder, Thure Adler, Birgit Rathkolb, Jan Rozman, Anna-Lena Schütz, Cornelia Prehn, Michel E. Mickael, Marco Weiergräber, Jerzy Adamski, Dirk H. Busch, Gerhard Ehninger, Anna Matynia, Walker S. Jackson, Eckhard Wolf, Helmut Fuchs, Valerie Gailus-Durner, Stefan Bonn, Martin Hrabě de Angelis, Dan Ehninger (2018) Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, p. E2348-E2357 Continue to DOI




Publications from other journals

Alana M. Thackray, Alzbeta Cardova, Hanna Wolf, Lydia Pradl, Ina M Vorberg, Walker S. Jackson and Raymond Bujdoso
Genetic human prion disease modelled in PrP transgenic Drosophila
Biochemical Journal

Walker S. Jackson and Lech Kaczmarczyk
Astonishing advances in mouse genetic tools for biomedical research
Schweizerische Medizinische Wochenschrift

Raymond Bujdoso, Matthias Landgraf, Walker S Jackson, and Alana M Thackray
Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response
World Journal of Virology

Walker S. Jackson and Clemens Krost
Peculiarities of prion diseases
PLoS Pathogens

Walker S. Jackson, Clemens Krost, Andrew W. Borkowski and Lech Kaczmarczyk
Translation of the Prion Protein mRNA Is Robust in Astrocytes but Does Not Amplify during Reactive Astrocytosis in the Mouse Brain

Walker S. Jackson
Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
Disease Models & Mechanisms

Walker S. Jackson, Andrew W. Borkowski, Nicki E. Watson, liver D. King, Henryk Faas, Alan Jasanoff and Susan Lindquist
Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice

Research area