Neurofibrillary tangles in Niemann-Pick disease type C

Kipuko Suzuki, Colette C. Parker, Peter G. Pentchev, David Katz, Bernardino Ghetti, Anthony N. D'Agostino, Eugene D. Carstea

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Niemann-Pick disease type C (NPC) is an autosomal recessive disease, belonging to a clinically heterogeneous group of lipid storage diseases, distinguished by a unique error in cellular trafficking of exogenous cholesterol, associated with lysosomal accumulation of unesterified cholesterol. Unlike Niemann-Pick disease types A and B, there is no primary genetic defect in sphingomyelinase in NPC. During the routine neuropathological study of NPC patients, we found neurofibrillary tangles (NFT) in a series of cases with a slowly progressive chronic course. These were not associated with β-amyloid deposits. The NFT were most frequent in the orbital gyrus, cingulate gyrus and entorhinal region of the cerebral cortex, but were also frequently found in the basal ganglia, thalamus and hypothalamus. In one of the most severely affected case, the NFT were even found in the neurons in the inferior olivary nucleus and in the spinal cord. The NFT were immunostained with Alz 50, and cosisted of paired helical filaments. The distribution of the neurons bearing the NFT was generally similar to that of the swollen storage neurons, and storage neurons often contained NFT in their perikarya and/or in the meganeurites. However, neurons with NFT could be noted without swollen perikarya. The coexistence of neuronal storage and NFT in NPC without amyloid deposits suggests that perturbed cholesterol metabolism and/or lysosomal membrane trafficking may play a role in the formation of NFT, and that amyloid deposits are not necessarily the prerequisite for NFT formation. The results of our study also suggest that NFT formation may be a rather nonspecific cellular reaction of neurons to certain slowly progressive metabolic perturbations of an as yet undefined nature.

Original languageEnglish
Pages (from-to)227-238
Number of pages12
JournalActa Neuropathologica
Volume89
Issue number3
DOIs
StatePublished - Mar 1995

Fingerprint

Type C Niemann-Pick Disease
Neurofibrillary Tangles
Neurons
Amyloid Plaques
Cholesterol
Type B Niemann-Pick Disease
Type A Niemann-Pick Disease
Olivary Nucleus
Sphingomyelin Phosphodiesterase
Gyrus Cinguli
Basal Ganglia
Prefrontal Cortex
Thalamus
Cerebral Cortex
Hypothalamus
Spinal Cord

Keywords

  • Cholesterol metabolism
  • Lysosomal disease
  • Neuronal storage disease
  • Paired helical filaments
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Suzuki, K., Parker, C. C., Pentchev, P. G., Katz, D., Ghetti, B., D'Agostino, A. N., & Carstea, E. D. (1995). Neurofibrillary tangles in Niemann-Pick disease type C. Acta Neuropathologica, 89(3), 227-238. https://doi.org/10.1007/BF00309338

Neurofibrillary tangles in Niemann-Pick disease type C. / Suzuki, Kipuko; Parker, Colette C.; Pentchev, Peter G.; Katz, David; Ghetti, Bernardino; D'Agostino, Anthony N.; Carstea, Eugene D.

In: Acta Neuropathologica, Vol. 89, No. 3, 03.1995, p. 227-238.

Research output: Contribution to journalArticle

Suzuki, K, Parker, CC, Pentchev, PG, Katz, D, Ghetti, B, D'Agostino, AN & Carstea, ED 1995, 'Neurofibrillary tangles in Niemann-Pick disease type C', Acta Neuropathologica, vol. 89, no. 3, pp. 227-238. https://doi.org/10.1007/BF00309338
Suzuki K, Parker CC, Pentchev PG, Katz D, Ghetti B, D'Agostino AN et al. Neurofibrillary tangles in Niemann-Pick disease type C. Acta Neuropathologica. 1995 Mar;89(3):227-238. https://doi.org/10.1007/BF00309338
Suzuki, Kipuko ; Parker, Colette C. ; Pentchev, Peter G. ; Katz, David ; Ghetti, Bernardino ; D'Agostino, Anthony N. ; Carstea, Eugene D. / Neurofibrillary tangles in Niemann-Pick disease type C. In: Acta Neuropathologica. 1995 ; Vol. 89, No. 3. pp. 227-238.
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