Frontal Lobe Dementia With Novel Tauopathy: Sporadic Multiple System Tauopathy With Dementia

• Published in: Journal of neuropathology and experimental neurology Vol. 60; no. 4; pp. 328 - 341
• Main Authors: BIGIO, EILEEN H, LIPTON, ANNE M, YEN, SHU-HUI, HUTTON, MIKE L, BAKER, MATT, NACHARAJU, PARIMALA, WHITE, CHARLES L, DAVIES, PETER, LIN, WENLANG, DICKSON, DENNIS W
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01-04-2001; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Aged; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Dementia - diagnosis; Dementia - metabolism; Dementia - physiopathology; Dementia, Vascular - diagnosis; Diagnosis, Differential; Disease Progression; Electroencephalography; Fatal Outcome; Female; Frontal Lobe - metabolism; Frontal Lobe - pathology; Frontal Lobe - physiopathology; Humans; Inclusion Bodies - metabolism; Inclusion Bodies - pathology; Magnetic Resonance Imaging; Medical sciences; Neuroglia - metabolism; Neuroglia - pathology; Neurology; Neurons - metabolism; Neurons - pathology; Parietal Lobe - metabolism; Parietal Lobe - pathology; Pick Disease of the Brain - diagnosis; tau Proteins - metabolism; Temporal Lobe - metabolism; Temporal Lobe - pathology; Human; Immunohistochemistry; Nervous system diseases; Frontal lobe; Sporadic; Clinical form; Electron microscopy; Cerebral disorder; Case study; Pathology; Tau protein; Central nervous system disease; Degenerative disease; Dementia
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/60.4.328

We present a novel tauopathy in a patient with a 10-yr history of progressive frontal lobe dementia and a negative family history. Autopsy revealed mild atrophy of frontal and parietal lobes and severe atrophy of the temporal lobes. There were occasional filamentous tau-positive inclusions, but more interesting were numerous distinctive globular neuronal and glial tau-positive inclusions in both gray and white matter of the neocortex. Affected subcortical regions included substantia nigra, globus pallidus, subthalamic nucleus, and cerebellar dentate nucleus, in a distribution similar to progressive supranuclear palsy (PSP), but without significant accompanying neuronal loss or gliosis. Predominantly straight filaments were detected by electron microscopy (EM), while other inclusions were similar to fingerprint bodies. No twisted ribbons were detected. Immuno-EM studies revealed that only the filamentous inclusions were composed of tau. Immunoblotting of sarkosyl-insoluble tau revealed 2 major bands of 64 and 68 kDa. Blotting analysis after dephosphorylation revealed predominantly 4-repeat tau. Sequence analysis of tau revealed that there were no mutations in either exons 9–13 or the adjacent intronic sequences. The unique cortical tau pathology in this case of sporadic multiple system tauopathy with dementia adds a new pathologic profile to the spectrum of tauopathies.