TY - JOUR
T1 - Neuropathology of the hippocampus in FTLD-Tau with Pick bodies
T2 - a study of the BrainNet Europe Consortium
AU - Kovacs, G. G.
AU - Rozemuller, A. J. M.
AU - van Swieten, J. C.
AU - Gelpi, E.
AU - Majtenyi, K.
AU - Al-Sarraj, Safa
AU - Troakes, C.
AU - Bodi, I.
AU - King, A.
AU - Hortobagyi, T.
AU - Esiri, M. M.
AU - Ansorge, O.
AU - Giaccone, G.
AU - Ferrer, I.
AU - Arzberger, T.
AU - Bogdanovic, N.
AU - Nilsson, T.
AU - Leisser, I.
AU - Alafuzoff, I.
AU - Ironside, J. W.
AU - Kretzschmar, H.
AU - Budka, H.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - alpha-synuclein
KW - frontotemporal lobar degeneration
KW - Pick's disease
KW - Tau
KW - TDP-43
KW - unclassifiable tauopathy
KW - FRONTOTEMPORAL LOBAR DEGENERATION
KW - PROGRESSIVE SUPRANUCLEAR PALSY
KW - PLAQUE DYSTROPHIC DENDRITES
KW - NEURODEGENERATIVE DISEASES
KW - CORTICOBASAL DEGENERATION
KW - ALZHEIMERS-DISEASE
KW - MONOCLONAL-ANTIBODIES
KW - WHITE-MATTER
KW - INCLUSIONS
KW - DEMENTIA
U2 - 10.1111/j.1365-2990.2012.01272.x
DO - 10.1111/j.1365-2990.2012.01272.x
M3 - Article
SN - 0305-1846
VL - 39
SP - 166
EP - 178
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
IS - 2
ER -