title: Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.
abstract: Frontotemporal lobar degeneration (FTLD) is an umbrella term for a heterogeneous group of young-onset dementias of uncertain prevalence and incidence worldwide. Atypical cases of FTLD with fused in sarcoma inclusions (aFTLD-U) have been described recently, but their molecular characterization is still due. Using shotgun mass spectrometry, we identified a total of 107 differentially expressed proteins in the prefrontal cortex, cerebellum and occipital lobe from aFTLD-U patients compared to controls. These proteins are involved in a range of biological pathways such as cellular transport in the prefrontal cortex, energy metabolism in the cerebellum, and protein metabolism in the occipital lobe. In addition, they were validated by selective reaction monitoring (SRM). Comparison of the aFTLD-U proteomic findings with similar studies of Alzheimer's disease and schizophrenia led to identification of proteins that may be related to dementias and psychoses, respectively. Further studies of aFTLD-U and other FTLD subtypes are warranted, although this will require intensive biobanking efforts.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.forename: David M
authors.initials: DM
authors.lastname: Mann
authors.forename: Sigrun
authors.initials: S
authors.lastname: Roeber
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.forename: Corinna
authors.initials: C
authors.lastname: Bauder
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
authors.forename: Benedikt
authors.initials: B
authors.lastname: Volk
authors.forename: Atik
authors.initials: A
authors.lastname: Baborie
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D004734:Energy Metabolism; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009778:Occipital Lobe / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000737:chemistry / Q000378:metabolism*; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric; D049490:Systems Biology
chemical_list: D020543:Proteome