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CSF pro-orexin and amyloid-β38 expression in Alzheimer's disease and frontotemporal dementia

Heywood, WE; Hallqvist, J; Heslegrave, AJ; Zetterberg, H; Fenoglio, C; Scarpini, E; Rohrer, JD; ... Mills, K; + view all (2018) CSF pro-orexin and amyloid-β38 expression in Alzheimer's disease and frontotemporal dementia. Neurobiology of Aging , 72 pp. 171-176. 10.1016/j.neurobiolaging.2018.08.019. Green open access

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Abstract

There is an unmet need for markers that can stratify different forms and subtypes of dementia. Because of similarities in clinical presentation, it can be difficult to distinguish between Alzheimer's disease (AD) and frontotemporal dementia (FTD). Using a multiplex targeted proteomic LC-MS/MS platform, we aimed to identify cerebrospinal fluid proteins differentially expressed between patients with AD and FTD. Furthermore analysis of 2 confirmed FTD genetic subtypes carrying progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72) mutations was performed to give an insight into the differing pathologies of these forms of FTD. Patients with AD (n = 13) demonstrated a significant (p < 0.007) 1.24-fold increase in pro-orexin compared to FTD (n = 32). Amyloid beta-38 levels in patients with AD were unaltered but demonstrated a >2-fold reduction (p < 0.0001) in the FTD group compared to controls and a similar 1.83-fold reduction compared to the AD group (p < 0.001). Soluble TREM2 was elevated in both dementia groups but did not show any difference between AD and FTD. A further analysis comparing FTD subgroups revealed slightly lower levels of proteins apolipoprotein E, CD166, osteopontin, transthyretin, and cystatin C in the GRN group (n = 9) compared to the C9orf72 group (n = 7). These proteins imply GRN FTD elicits an altered inflammatory response to C9orf72 FTD.

Type: Article
Title: CSF pro-orexin and amyloid-β38 expression in Alzheimer's disease and frontotemporal dementia
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neurobiolaging.2018.08.019
Publisher version: http://dx.doi.org/10.1016/j.neurobiolaging.2018.08...
Language: English
Additional information: This article is published under a Creative Commons licence (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Keywords: Alzheimer's disease, Amyloid β-38, C9orf72, Frontotemporal dementia, Orexin, Progranulin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10058347
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