Diffuse neurofibrillary tangles with calcification (Kosaka–Shibayama disease) in Japan

Abstract

Diffuse neurofibrillary tangles with calcification (DNTC) is a rare, pre-senile type of dementia. The term 'DNTC' was initially proposed by Kosaka in 1994. Although 26 autopsies and 21 clinical patients with DNTC have been described in Japan to date, DNTC has rarely been reported in the European and North American published work. We speculate that DNTC has been overlooked in other countries.Herein, we review all known reports of DNTC in Japan and propose clinical diagnostic criteria for DNTC.

Idiopathic basal ganglia calcification (Fahr's disease) and dementia

“…In the current issue of Psychiatry and Clinical Neurosciences, Ukai and Kosaka have presented findings from a comprehensive review of the literature on diffuse neurofibrillary tangles with calcification (DNTC, Kosaka–Shibayama disease), a form of early‐onset dementia, and have proposed a tentative clinical diagnostic criteria for DNTC. Indeed, Dr Kenji Kosaka, one of the authors of the article, has played a major role in discovering and establishing the clinicopathological entity of DNTC since the 1970s, as he has done also for dementia with Lewy bodies .…”

“…Indeed, Dr Kenji Kosaka, one of the authors of the article, has played a major role in discovering and establishing the clinicopathological entity of DNTC since the 1970s, as he has done also for dementia with Lewy bodies . According to the criteria presented in the article, the presence of dementia and Fahr‐type IBGC is sufficient to support the clinical diagnosis of ‘possible DNTC,’ and both of the features accompanied by frontotemporal syndrome or localized atrophy of the bilateral temporal or frontotemporal lobes on CT/magnetic resonance imaging are sufficient to support the clinical diagnosis of ‘probable DNTC.’ Neuropathologically, DNTC is characterized by the presence of abundant neurofibrillary tangles (NFT) with similar distribution and identical biochemical and immunochemical features to NFT in the brains of Alzheimer's disease patients, where NFT contain 3‐ and 4‐repeat tau. Although very few senile plaques or amyloid β deposits are found in the brain, multiple proteinopathies are evident in DNTC.…”

“…Although very few senile plaques or amyloid β deposits are found in the brain, multiple proteinopathies are evident in DNTC. Indeed, not only NFT but also glial fibrillary tangles of tau pathology as well as α‐synucleinopathy and TDP‐43 proteinopathy are observed in a large proportion of patients with DNTC …”

“…Moreover, there are several familial and sporadic IBGC patients carrying the mutation in the SLC20A2 and PDGFB genes whose onset symptom was dementia, with brain imaging showing frontotemporal atrophy or frontotemporal hypoperfusion . Ukai and Kosaka have raised concerns that there might be occult DNTC among patients previously reported as having ‘Fahr's disease with dementia.’ Taken together, these findings indicate possibilities that the pathomechanisms of DNTC, at least in part, might be associated with the specific dysfunction caused by the genetic defects of familial IBGC. In this context, it is noteworthy that the XPR1 gene variants or expression changes are associated with phenotypes observed in schizophrenia, Alzheimer's disease, and amyotrophic lateral sclerosis/frontotemporal lobar degeneration .…”

“…Indeed, not only NFT but also glial fibrillary tangles of tau pathology as well as α-synucleinopathy and TDP-43 proteinopathy are observed in a large proportion of patients with DNTC. 2 Although there have been no reports of the familial form of DNTC in the literature, mutations in the SLC20A2, PDGFRB, and PDGFB genes have also been found in 'sporadic' patients with IBGC. 5 Cognitive impairment is observed commonly in 64.7%, 40.0%, and 54.6% of the mutation carriers of the SLC20A2, PDGFRB, and PDGFB genes, respectively.…”