1. FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration
- Author
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Urwin, Hazel, Josephs, Keith A, Rohrer, Jonathan D, Mackenzie, Ian R, Neumann, Manuela, Authier, Astrid, Seelaar, Harro, Van Swieten, John C, Brown, Jeremy M, Johannsen, Peter, Nielsen, Jorgen E, Holm, Ida E, FReJA Consortium, Dickson, Dennis W, Rademakers, Rosa, Graff-Radford, Neill R, Parisi, Joseph E, Petersen, Ronald C, Hatanpaa, Kimmo J, White, Charles L, Weiner, Myron F, Geser, Felix, Van Deerlin, Vivianna M, Trojanowski, John Q, Miller, Bruce L, Seeley, William W, van der Zee, Julie, Kumar-Singh, Samir, Engelborghs, Sebastiaan, De Deyn, Peter P, Van Broeckhoven, Christine, Bigio, Eileen H, Deng, Han-Xiang, Halliday, Glenda M, Kril, Jillian J, Munoz, David G, Mann, David M, Pickering-Brown, Stuart M, Doodeman, Valerie, Adamson, Gary, Ghazi-Noori, Shabnam, Fisher, Elizabeth MC, Holton, Janice L, Revesz, Tamas, Rossor, Martin N, Collinge, John, Mead, Simon, and Isaacs, Adrian M
- Subjects
Adult ,Male ,Aging ,Clinical Trials and Supportive Activities ,Clinical Sciences ,FTLD-UPS ,tau Proteins ,Neurodegenerative ,Alzheimer's Disease ,Hippocampus ,FReJA Consortium ,Rare Diseases ,Clinical Research ,mental disorders ,Acquired Cognitive Impairment ,Genetics ,Prevalence ,2.1 Biological and endogenous factors ,Humans ,Aetiology ,Age of Onset ,Alzheimer's Disease Related Dementias (ADRD) ,FUS ,Dyskinesias ,Neurology & Neurosurgery ,Mental Disorders ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,nutritional and metabolic diseases ,FTD ,DNA ,Middle Aged ,Brain Disorders ,nervous system diseases ,Frontal Lobe ,DNA-Binding Proteins ,Frontotemporal Dementia (FTD) ,Neurological ,Mutation ,RNA-Binding Protein FUS ,Dementia ,Female ,Frontotemporal ,Frontotemporal Lobar Degeneration ,FTLD ,Sequence Analysis - Abstract
Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated.
- Published
- 2010