SERUM FERRITIN IS INCREASED IN A SUBSET OF PATIENTS WITH FRONTOTEMPORAL DEMENTIA

Abstract

Frontotemporal dementia (FTD) is a common cause of early-onset dementia. Recent studies have shown a role for inflammation and an altered immune response in FTD. Serum levels of ferritin, an iron carrier and storage protein, are increased in inflammatory disorders and can therefore be a surrogate marker of inflammation. In this study we aimed to evaluate whether serum ferritin levels are increased in patients with FTD. Using a latex fixation test we measured ferritin levels in serum samples of 133 patients meeting diagnostic criteria for an FTD spectrum disorder (60 behavioural variant FTD, 6 FTD with motor neurone disease (MND), 23 semantic variant primary progressive aphasia (PPA), 31 nonfluent variant PPA, 8 PPA-not otherwise specified, 4 with corticobasal syndrome/progressive supranuclear palsy, 1 with inclusion body myositis with Paget's disease and FTD) as well as 16 patients with logopenic variant PPA and 26 healthy controls. Pathological and genetic status (presence of GRN, C9orf72, MAPT, TBK1, VCP, SQSTM1mutations) was noted when available. No significant difference in age or gender was seen between the groups. Mean (standard deviation) ferritin levels (ng/ml) in the FTD group were 115.4 (111.0), 113.0 (85.5) in the logopenic variant PPA group and 80.7 (55.2) in the controls. Although there was no significant difference between the disease groups there was a subset of patients with FTD with very high ferritin levels. Stratifying the FTD cohort according to clinical diagnosis, patients with FTD-MND (134.9 (136.5)) had the highest levels. 40 patients had tested positive for genetic mutations: the GRN mutation group (n=9) had the highest ferritin levels (164.5 (186.3), followed by individuals with C9orf72(n=16) mutations (115.9 (129.8)). Combining genetic and pathological cases, levels were higher in those with definite or likely TDP-43 pathology (n=29: 142.0 (149.1)) compared to individuals with tau pathology (n=13: 96.3 (79.0)). Ferritin concentration did not correlate with disease duration in any of the groups. This study shows a trend for increased serum ferritin levels in FTD, particularly in those with TDP-43opathies, including those clinically with FTD-MND and genetically with GRN and C9orf72 mutations. This study adds further evidence for the role of inflammation in FTD.