Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies

M. L. Schmidt, J. Murray, V. M.Y. Lee, William D Hill, A. Wertkin, J. Q. Trojanowski

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

A subset of demented elderly patients exhibit large numbers of cortical intraneuronal inclusions similar to the neurofilament (NF)-rich Lewy bodies (LB) found in pigmented subcortical neurons of patients with Parkinson's disease (PD). Because these cortical inclusions may contribute to the emergence of cognitive impairments in afflicted individuals, the authors mapped the distribution of NF epitopes in these so-called cortical LBs. This was done using ethanol-fixed tissues and a large library of monoclonal antibodies (MAbs) with well-characterized binding specificities to various regions of each NF triplet protein. Cortical LBs were examined by light, confocal, and electron microscopy, and they were compared with the subcortical LBs of PD and LBs in the peripheral nervous system (PNS). Monoclonal antibodies specific for the rod regions of each of the three NF subunits, or for phosphate-dependent and independent antigenic sites in the tail region of the high- (NF-H) and middle- (NF-M) molecular weight (M(r)) NF subunits as well as other MAbs to the extreme COOH terminus of NF-L and NF-M or the head region of NF-M labeled a variable number of cortical LBs. Remarkably one of these anti-NF MAbs, RMO32, which recognized a phosphorylated epitope in the tail region of NF-M, immunolabeled nearly all cortical LBs, whereas each of the other anti-NF MAbs never labeled more than 10% of ubiquitin- or RMO32-positive cortical LBs. Further LBs in the PNS resembled those in the central nervous system (CNS) in their immunologic properties, and LBs in both sites were dominated by filamentous aggregates at the ultrastructural level. These findings suggest that NF proteins are profoundly altered during their incorporation into cortical and PNS LBs. Further the authors here identified immunologic and ultrastructural properties common to cortical LBs, PNS LBs, and classic substantia nigra LBs in PD. The accumulation of filamentous, perikaryal inclusions rich in NF proteins at diverse sites in the CNS and PNS of patients with a variety of neurodegenerative disorders suggests a widespread disruption of NF metabolism or transport.

Original languageEnglish (US)
Pages (from-to)53-65
Number of pages13
JournalAmerican Journal of Pathology
Volume139
Issue number1
StatePublished - Jan 1 1991

Fingerprint

Neurofilament Proteins
Lewy Bodies
Intermediate Filaments
Peripheral Nervous System
Epitopes
Monoclonal Antibodies
Parkinson Disease
Protein Domains
Central Nervous System
Substantia Nigra
Ubiquitin
Confocal Microscopy
Neurodegenerative Diseases
Electron Microscopy
Ethanol

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Schmidt, M. L., Murray, J., Lee, V. M. Y., Hill, W. D., Wertkin, A., & Trojanowski, J. Q. (1991). Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. American Journal of Pathology, 139(1), 53-65.

Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. / Schmidt, M. L.; Murray, J.; Lee, V. M.Y.; Hill, William D; Wertkin, A.; Trojanowski, J. Q.

In: American Journal of Pathology, Vol. 139, No. 1, 01.01.1991, p. 53-65.

Research output: Contribution to journalArticle

Schmidt, ML, Murray, J, Lee, VMY, Hill, WD, Wertkin, A & Trojanowski, JQ 1991, 'Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies', American Journal of Pathology, vol. 139, no. 1, pp. 53-65.
Schmidt ML, Murray J, Lee VMY, Hill WD, Wertkin A, Trojanowski JQ. Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. American Journal of Pathology. 1991 Jan 1;139(1):53-65.
Schmidt, M. L. ; Murray, J. ; Lee, V. M.Y. ; Hill, William D ; Wertkin, A. ; Trojanowski, J. Q. / Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. In: American Journal of Pathology. 1991 ; Vol. 139, No. 1. pp. 53-65.
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