Fourth International Symposium on Neuroacanthocytosis

Abstracts from the Fourth International Symposium on Neuroacanthocytosis

July 1-2, 2008
London and Oxford

Chairs: Prof. Kailash Bhatia, MD, FRCP, Institute of Neurology, University College London; Prof. Anthony P. Monaco, MD, PhD, Wellcome Trust Centre for Human Genetics, University of Oxford

Organizers: Antonio Velayos-Baeza, PhD; Susanne Schneider, MD; Glenn Irvine

1-6 Chorein expression and neuropathology
B. Bader
Neurologische Klinik, Ludwig-Maximilians-Universität, D-81366, Munich, Germany

Background: Chorea-acanthocytosis (ChAc) is characterised by marked neurodegeneration within the caudate nucleus and presence of malformed erythrocytes. The connection between both phenomena and the underlying function of the mutated protein chorein remain still cryptic. For progress in understanding the disease, understanding the functional aspects is crucial.
Methods: Brain tissue of ChAc patients in comparison to Huntington's disease (HD) patients was investigated by histology, immunohistochemistry and stereology for 3D reconstruction as well as morphometric methods for cell differentiation and calculation. Western blot was used to study chorein expression in various brain regions as well as peripheral tissues of healthy subjects. Further, blood samples of HD and pantothenate-kinase associated neurodegeneration (PKAN) have been examined for chorein presence in erythrocyte membranes.
Results: In ChAc a notable loss of neurons was found in neocortex and even more striking in striatum, exceeding the observations in late stage HD brains in these regions. Impressive neurodegeneration was confirmed by both, a remarkable astrogliosis and an increased number of activated microglial cells. This could also be documented by an increase in the astroglia/neuron-index in ChAc (47) and in HD (23) compared to healthy controls (3). In Western blot, chorein expression was throughout constant in different brain regions of healthy control subjects, but was absent in all corresponding tissues of ChAc patients. Two fragments present in healthy brain and missing in ChAc tissue are recognised at 160 kDa and 100 kDa.
Furthermore, we examined different peripheral tissues of healthy control subjects and found full length chorein synthesised in brain, blood, testis and muscle. Comparing brain and peripheral tissues, chorein expression pattern seems to be tissue specific. While full length chorein is missing in erythrocyte membranes of ChAc patients, it is present in all healthy controls examined so far (n > 30), as well as in five HD patients (PKAN results pending).
Conclusions: Neurodegeneration in ChAc is different than in HD regarding the degree of tissue loss and astroglia/neuron index but shows similarities regarding the affected brain regions, while chorein is expressed ubiquitously in non affected brains. Results also point out that different variants of chorein are synthesised in brain tissue. This can implicate a structural organisation of functional domains within the chorein protein. Chorein presence in erythrocytes of healthy controls and patients suffering of similar disorders supports the specificity of the diagnostic Western blot.