{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:31:54Z","timestamp":1790537514864,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T00:00:00Z","timestamp":1478044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000368","name":"Brain Research Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Mutations in the TANK\u2010binding kinase 1 (<jats:italic>TBK1<\/jats:italic>) gene have recently been shown to cause frontotemporal dementia (FTD). However, the phenotype of <jats:italic>TBK1<\/jats:italic>\u2010associated FTD is currently unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a single case longitudinal study of a patient who was subsequently found to have a novel A705fs mutation in the <jats:italic>TBK1<\/jats:italic> gene. He was assessed annually over a 7\u2010year period with a series of clinical, cognitive, and magnetic resonance imaging assessments. His brain underwent pathological examination at postmortem.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient presented at the age of 64\u00a0years with an 18\u2010month history of personality change including increased rigidity and obsessiveness, apathy, loss of empathy, and development of a sweet tooth. His mother had developed progressive behavioral and cognitive impairment from the age of 57\u00a0years. Neuropsychometry revealed intact cognition at first assessment. Magnetic resonance imaging showed focal right temporal lobe atrophy. Over the next few years his behavioral problems progressed and he developed cognitive impairment, initially with anomia and prosopagnosia. Neurological examination remained normal throughout without any features of motor neurone disease. He died at the age of 72\u00a0years and postmortem showed TDP\u201043 type A pathology but with an unusual novel feature of numerous TAR DNA\u2010binding protein 43 (TDP\u201043)\u2013positive neuritic structures at the cerebral cortex\/subcortical white matter junction. There was also associated argyrophilic grain disease not previously reported in other <jats:italic>TBK1<\/jats:italic> mutation cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p><jats:italic>TBK1<\/jats:italic>\u2010associated FTD can be associated with right temporal variant FTD with progressive behavioral change and relatively intact cognition initially. The case further highlights the benefits of next\u2010generation sequencing technologies in the diagnosis of neurodegenerative disorders and the importance of detailed neuropathologic analysis.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.dadm.2016.10.003","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T02:30:27Z","timestamp":1478140227000},"page":"75-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The clinical, neuroanatomical, and neuropathologic phenotype of <i>TBK1<\/i>\u2010associated frontotemporal dementia: A longitudinal case report"],"prefix":"10.1002","volume":"6","author":[{"given":"Carolin A.M.","family":"Koriath","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Disease, MRC Prion Unit UCL Institute of Neurology London 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