Neuropathology Case Cluster: Neuropathology of focal cortical, behavioral, and psychiatric syndromes in neurodegenerative diseases (neuropathology cluster case 14–32)

Although recent advances in molecular biological studies of neurodegenerative diseases have been remarkable, it is still difficult to fully explain the diversity of neuropsychiatric symptoms and clinical progression in individual cases. Moreover, it is rare for a clinician to observe the long-term course of neurodegenerative diseases and to verify the correlation of neuropsychiatric symptoms with their neuropathological findings. Traditionally, in Japan, dedicated psychiatrists and neurologists have made great efforts to evaluate the heterogeneity of these neuropsychiatric symptoms neuropathologically as well as neuropsychologically. Herein, neurodegenerative diseases with primary progressive aphasia or late-onset psychosis that have recently attracted attention in clinical settings are presented as sequels to the Neuropathological Case Cluster (NCC), inaugurated in Neuropathology. NCC will increase the significance of case reports by contrasting multiple cases and encourage many researchers to report case series. Kawakatsu et al. reported four patients (NCC #14–17) with semantic dementia (SD) with transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, showing diversity in neuropsychological, neuroimaging, and comorbid neuropathology. They demonstrated that patients with early-onset SD had TDP-type C pathology, consistent with previous reports, while patients with lateonset SD had TDP-type A pathology. Furthermore, they discussed the possibility that late-onset SD may be difficult to differentiate from limbic-predominant age-related TDP-43 encephalopathy (LATE). For the left–right asymmetry of lesions, TDP pathology was more abundant on the less atrophic side than on the more atrophic side. SD is relatively more common in Asian countries than in Western countries, which is probably due to genetic differences. However, clinicopathological studies on SD are still limited in Asian countries, and this report may facilitate future research. Ishihara et al. reported two patients (NCC #18, 19) with progressive speech disorder accompanied by peculiar neuropsychological symptoms and examined their correspondence with neuropathological lesion distribution in detail. Case 1 involved amyotrophic lateral sclerosis with dementia presenting with frontal lobe agraphia corresponding to the left middle frontal lesion. Case 2 exhibited Pick’s disease presenting with ideomotor and limb-kinetic apraxia in addition to apraxia of speech. Superficial spongiosis, neuronal loss, Pick bodies, and Pick cells were observed in the areas corresponding to the respective sources of lesions. They concluded that the topographic distribution of the cerebral cortical pathologies along with the degree of changes, not the nature of pathological changes, determine the corresponding clinical features. Kawakami et al. reported two elderly patients (NCC #20, 21) with unclassified tau pathology in the limbic regions presenting with psychiatric symptoms and behavioral disturbances. The pathology of Case 1 was partially consistent with primary age-related tauopathy (PART) and age-related tau astrogliopathy, but there were 3-repeat tau-positive neuronal cytoplasmic inclusions in the striatum and thorn-shaped astrocytes in the amygdala. Case 2 had a PART-like pathology with 4-repeat taupositive oligodendroglial inclusions in the medial temporal cortex. They concluded that tau pathology might be associated with specific psychiatric symptoms, and the importance of pathological investigation of psychiatric disorders in older patients should be recognized. Yokota et al. reported 11 patients (NCC #22–32) with 4-repeat tauopathies presenting with psychiatric disorders, whose age at onset varied from 32 to 88 years. Out of 11 patients, nine had argyrophilic grain disease (AGD), one had atypical progressive supranuclear palsy Correspondence: Shinobu Kawakatsu, Department of Neuropsychiatry, Aizu Medical Center, Fukushima Medical University, 21-2 Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, Fukushima 969-3492, Japan. Email: kshinobu@fmu.ac. jp