Neuropathology of the hippocampus in FTLD‐Tau with Pick bodies: a study of the BrainNet Europe Consortium

Abstract

G. G. Kovacs, A. J. M. Rozemuller, J. C. van Swieten, E. Gelpi, K. Majtenyi, S. Al‐Sarraj, C. Troakes, I. Bódi, A. King, T. Hortobágyi, M. M. Esiri, O. Ansorge, G. Giaccone, I. Ferrer, T. Arzberger, N. Bogdanovic, T. Nilsson, I. Leisser, I. Alafuzoff, J. W. Ironside, H. Kretzschmar and H. Budka (2013) Neuropathology and Applied Neurobiology39, 166–178 Neuropathology of the hippocampus in FTLD‐Tau with Pick bodies: a study of the BrainNet Europe Consortium Aims: Frontotemporal lobar degeneration with Pick bodies (Pick's disease) is characterized by the presence of tau immunoreactive spherical structures in the cytoplasm of neurones. In view of confusion about the molecular pathology of Pick's disease, we aimed to evaluate the spectrum of tau pathology and concomitant neurodegeneration‐associated protein depositions in the characteristically affected hippocampus. Methods: We evaluated immunoreactivity (IR) for tau (AT8, 3R, 4R), α‐synuclein, TDP43, p62, and ubiquitin in the hippocampus, entorhinal and temporal cortex in 66 archival cases diagnosed neuropathologically as Pick's disease. Results: Mean age at death was 68.2 years (range 49–96). Fifty‐two (79%) brains showed 3R immunoreactive spherical inclusions in the granule cells of the dentate gyrus. These typical cases presented mainly with the behavioural variant of frontotemporal dementia, followed by progressive aphasia, mixed syndromes or early memory disturbance. α‐Synuclein IR was seen only in occasional spherical tau‐positive inclusions, TDP‐43 IR was absent, and 4R IR was present only as neurofibrillary tangles in pyramidal neurones. Aβ IR was observed in 16 cases; however, the overall level of Alzheimer's disease‐related alterations was mainly low or intermediate (n = 3). Furthermore, we identified six cases with unclassifiable tauopathy. Conclusions: (i) Pick's disease may occur also in elderly patients and is characterized by a relatively uniform pathology with 3R tau inclusions particularly in the granule cells of dentate gyrus; (ii) even minor deviation from these morphological criteria suggests a different disorder; and (iii) immunohistological revision of archival cases expands the spectrum of tauopathies that require further classification.

Original article Hemimegalencephaly: foetal tauopathy with mTOR hyperactivation and neuronal lipidosis

“…The histopathological features in the hemimegalencephalic hemisphere were similar in all three cases and to other cases previously described by us and Hemimegalencephaly: foetal tauopathy with mTOR hyperactivation and neuronal lipidosis by other authors [18,26,44,48]. Gyral formation of the cortex was abnormal, corresponding in various regions to pachygyria, polymicrogyria and pseudogyri (i.e.…”

“…The neuropathological character of phosphorylated tau in our cases of HME is different from the tau expressed in adult neurodegenerative diseases. In the latter, the tau appears as crescent-shaped structures in the cytoplasm of the neuronal and some glial somata, but the intense white matter axonal immunoreactivity with beaded neurites is not characteristic [26]. However, the neocortical layer of most severe neuronal loss and in adult tauopathies is layer 2 [34] and the phosphorylated tau expression in all of our infantile cases of HME was also in the superficial laminae of the cortex, showing a similar gradient within the cortex.…”

Deep clinical and neuropathological phenotyping of Pick disease

“…Although this is one of the largest and most well-annotated PiD autopsy cohorts reported the number of patients in each phase was relatively small in comparison to more common neurodegenerative diseases 47, 48 . One series of PiD cases included >50 cases, but examined only the hippocampus 49 . Our cases were evaluated by tertiary academic centers, and thus there may be referral bias for atypical or severe disease.…”

Atypical association of semantic dementia, corticobasal syndrome, and 4R tauopathy

“…Ballooned neurons are not distinctive and their absence or rarity does not preclude the diagnosis of CBD (Dickson et al, 2002;Wakabayashi & Takahashi, 2004). 4R-tau-positive Pick body-like inclusions have already been associated with several conditions, including CBD and PSP (Armstrong, Cairns, & Lantos, 2000;Ikeda, Akiyama, Arai, & Tsushiya, 2002;Kovacs & Budka, 2010;Kovacs et al, 2012;Miki, Mori, Hori, Kaimori, & Wakabayashi, 2009). In our case, the main neuropathological features consistent with CBD are the considerable cortical and subcortical involvement, the numerous astrocytic plaques and the extensive tau-immunoreactive cell processes in both gray matter and white matter (Armstrong et al, 2000;Dickson et al, 2002;Forman et al, 2002;Kouri, Murray, et al, 2011;Murray et al, 2007).…”