bioRxiv preprint doi: https://doi.org/10.1101/336842; this version posted June 2, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Ataxia Telangiectasia triggers deficits in Reelin pathway Júlia Canet-Pons1, Ralf Schubert2#, Ruth Pia Duecker2, Roland Schrewe2, Sandra Wölke2, ‡ ‡ Martina Schnölzer3, Georg Auburger1, Stefan Zielen2 , Uwe Warnken3 1 Exp. Neurology, 2 Division for Allergy, Pneumology and Cystic Fibrosis, Department for Children and Adolescence, Goethe University Medical School, 60590 Frankfurt am Main, 3 Functional Proteome Analysis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany # Correspondence to Ralf Schubert:
[email protected] ‡ These authors contributed equally to the work 1 bioRxiv preprint doi: https://doi.org/10.1101/336842; this version posted June 2, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Autosomal recessive Ataxia Telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the Ataxia-Telangiectasia-Mutated (ATM) gene, a serine-threonine protein kinase involved in DNA-damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood. Employing global proteomic profiling of cerebrospinal fluid from patients at ages around 15 years we detected reduced Calbindin, Reelin, Cerebellin-1, Cerebellin-3, Protocadherin Fat 2, Sempahorin 7A and increased Apolipoprotein -B, -H, -J peptides.