Journal
JOURNAL OF PROTEOME RESEARCH
Volume 11, Issue 4, Pages 2533-2543Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr2012279
Keywords
aFTLD; cerebellum; occipital lobe; prefrontal cortex; proteomics
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Funding
- Stanley Medical Research Institute
- Alzheimers Research UK
- Alzheimer's Society under the Brains for Dementia Research (BDR) initiative
- MRC
- Wellcome Trust
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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.
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