title: Tauopathy with hippocampal 4-repeat tau immunoreactive spherical inclusions: a report of three cases.
abstract: Tauopathies are a major group of neurodegenerative proteinopathies characterized by the accumulation of abnormal and hyperphosphorylated tau proteins in the brain. Tau pathology is characterized as 3R (repeat) or 4R predominant or mixed 3R and 4R type. Here we report three cases lacking mutations in the microtubule associated protein tau (MAPT) gene with unusual tau pathology. The age at onset and duration of illness, respectively, were 63 and 20 years (male), 67 and 5 years (female) and 72 and 20 years (female). The clinical presentation was compatible with a diagnosis of progressive supranuclear palsy (PSP) in two subjects and with cognitive decline in all three subjects. Common neuropathological features included neuronal loss in the hippocampus and dentate gyrus associated with spherical basophilic Pick body-like inclusions showing 4R tau immunoreactivity, which was supported by the detection of predominantly 4R tau species by Western blot examination. In addition, accumulation of tau immunoreactive argyrophilic astrocytes in the hippocampus and amygdala and oligodendroglial coiled bodies in the hippocampal white matter were observed. These morphologies appeared in combination with Alzheimer disease-related pathology and subcortical tau pathology compatible with PSP. Together with a single case report in the literature, our observations on these three cases expand the spectrum of previously described tauopathies. We suggest that this tauopathy variant with hippocampal 4R tau immunoreactive spherical inclusions might contribute to the cognitive deficits in the patients reported here. The precise definition of the clinicopathological relevance of these unusual tau pathologies merits further study.
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.|Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.
authors.forename: Linda K
authors.initials: LK
authors.lastname: Kwong
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.
authors.forename: John L
authors.initials: JL
authors.lastname: Robinson
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.
authors.forename: Eunran
authors.initials: E
authors.lastname: Suh
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Lee
authors.affiliation: Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D010641:Phenotype; D024801:Tauopathies / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: 4R tau isoform; Pick's disease; astroglia; hippocampus; tau; tauopathy