Neuronal Ubiquitinated Intranuclear Inclusions in Familial and Non-Familial Frontotemporal Dementia of the Motor Neuron Disease Type Associated with Amyotrophic Lateral Sclerosis

• Published in: Journal of neuropathology and experimental neurology Vol. 63; no. 8; pp. 801 - 811
• Main Authors: BIGIO, EILEEN H, JOHNSON, NANCY A, RADEMAKER, ALFRED W, FUNG, BING B, MESULAM, M-MARSEL, SIDDIQUE, NAILAH, DELLEFAVE, LISA, CALIENDO, JANICE, FREEMAN, STEFANIE, SIDDIQUE, TEEPU
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.08.2004; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Aged; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Biological and medical sciences; Dementia - genetics; Dementia - metabolism; Dementia - pathology; Female; Humans; Intranuclear Inclusion Bodies - genetics; Intranuclear Inclusion Bodies - metabolism; Intranuclear Inclusion Bodies - pathology; Male; Medical sciences; Middle Aged; Motor Neuron Disease - genetics; Motor Neuron Disease - metabolism; Motor Neuron Disease - pathology; Neurology; Neurons - metabolism; Neurons - pathology; Retrospective Studies; Statistics, Nonparametric; Ubiquitins - metabolism; Ubiquitin; Nervous system diseases; Inclusion; Familial dementia; Central nervous system disease; Motor neuron disease; Amyotrophic lateral sclerosis; Degenerative disease; Frontotemporal dementia; Spinal cord disease; Frontotemporal dementia of the motor neuron disease-type; Dementia
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/63.8.801

Ubiquitinated cytoplasmic inclusions (Ub-CIs) in superficial frontal cortex and dentate gyrus neurons are the hallmark of frontotemporal degeneration of the motor neuron disease-type (FTD-MND-type). To date, 2 reports have described intranuclear ubiquitinated inclusions (Ub-INIs) in 9 cases of familial FTD-MND-type (without clinical or pathologic motor neuron disease, MND). In the current study we found an additional 11 cases with Ub-INIs. We have identified for the first time among these cases 2 with a negative family history and 3 that have concomitant amyotrophic lateral sclerosis (ALS). The results of the present study i) confirm a previous report of significantly lower average brain weight and longer duration in cases with Ub-INIs, ii) reveal significantly greater striatal neuronal loss and gliosis in cases with intranuclear inclusions, and iii) demonstrate that intranuclear inclusions correlate with cytoplasmic inclusions and dystrophic neurites in frontal cortex and striatum but not in dentate gyrus. In addition, the current study confirms that Ub-INIs are found in familial FTD-MND-type, but also extends the presence of Ub-INIs to familial FTD-MND (with concomitant ALS), and probably also to non-familial FTD-MND-type.