Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease

Linda C. Cork, Nancy H. Sternberger, Ludwig A. Sternberger, Manuel F. Casanova, Robert G. Struble, Donald L. Price

Research output: Contribution to journalArticle

Abstract

Neurofibrillary tangles (NFT) are a hallmark of Alzheimer’s disease (AD), and their presence correlates with the presence of dementia. A major constituent of NFT is the insoluble paired helical filament which shares some antigenic relationships with normal cytoskeletal elements, particularly neurofilaments. If neurofilament proteins (200, 145-160, and 68 kilodaltons [kd]) participate in the formation of NFT, the distribution of these constituents might be expected to be abnormal. To examine this issue, we used immunocytochemical methods to localize phosphorylated and nonphosphorylated epitopes of neurofilament proteins in hippocampal neurons of controls and patients with AD. Normally, the 200-kd neurofilament protein is not phosphorylated in the perikarya of neurons. However, in AD, many pyramidal neurons contained immunoreactive phosphorylated neurofilaments. Patterns of immu- noreactivity (linear, flame-shaped, or skein-like within perikarya) greatly resembled the appearance of silver-stained NFT. This pattern of immunoreactivity was not present in hippocampal pyramidal neurons in controls, except in one aged patient in whom adjacent silver-stained sections revealed a few NFT. Patterns of immunoreactivity with antibodies for nonphosphorylated neurofilament proteins were similar in control and AD neurons. Our results indicate that some NFT are associated with abnormal distributions of high molecular weight phosphorylated neurofilament proteins. One domain of the 200-kd protein is believed to be a component of the side arms which link neurofilaments and interact with microtubules. Abnormal interactions of perikaryal neurofilaments could play a role in the genesis of NFT, and this abnormality of the cytoskeleton could contribute to the dysfunction of neurons at risk in AD.

Original languageEnglish (US)
Pages (from-to)56-64
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume45
Issue number1
StatePublished - 1986

Fingerprint

Neurofibrillary Tangles
Intermediate Filaments
Alzheimer Disease
Neurofilament Proteins
Antigens
Neurons
Pyramidal Cells
Silver
Cytoskeleton
Microtubules
Dementia
Epitopes
Antibodies

Keywords

  • Alzheimer’s disease
  • Cytoskeleton
  • Neurofibrillary tangles
  • Neurofilaments

ASJC Scopus subject areas

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

Cite this

Cork, L. C., Sternberger, N. H., Sternberger, L. A., Casanova, M. F., Struble, R. G., & Price, D. L. (1986). Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease. Journal of Neuropathology and Experimental Neurology, 45(1), 56-64.

Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease. / Cork, Linda C.; Sternberger, Nancy H.; Sternberger, Ludwig A.; Casanova, Manuel F.; Struble, Robert G.; Price, Donald L.

In: Journal of Neuropathology and Experimental Neurology, Vol. 45, No. 1, 1986, p. 56-64.

Research output: Contribution to journalArticle

Cork, LC, Sternberger, NH, Sternberger, LA, Casanova, MF, Struble, RG & Price, DL 1986, 'Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease', Journal of Neuropathology and Experimental Neurology, vol. 45, no. 1, pp. 56-64.
Cork LC, Sternberger NH, Sternberger LA, Casanova MF, Struble RG, Price DL. Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease. Journal of Neuropathology and Experimental Neurology. 1986;45(1):56-64.
Cork, Linda C. ; Sternberger, Nancy H. ; Sternberger, Ludwig A. ; Casanova, Manuel F. ; Struble, Robert G. ; Price, Donald L. / Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease. In: Journal of Neuropathology and Experimental Neurology. 1986 ; Vol. 45, No. 1. pp. 56-64.
@article{3847329574d146b19b8306832d4f9905,
title = "Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease",
abstract = "Neurofibrillary tangles (NFT) are a hallmark of Alzheimer’s disease (AD), and their presence correlates with the presence of dementia. A major constituent of NFT is the insoluble paired helical filament which shares some antigenic relationships with normal cytoskeletal elements, particularly neurofilaments. If neurofilament proteins (200, 145-160, and 68 kilodaltons [kd]) participate in the formation of NFT, the distribution of these constituents might be expected to be abnormal. To examine this issue, we used immunocytochemical methods to localize phosphorylated and nonphosphorylated epitopes of neurofilament proteins in hippocampal neurons of controls and patients with AD. Normally, the 200-kd neurofilament protein is not phosphorylated in the perikarya of neurons. However, in AD, many pyramidal neurons contained immunoreactive phosphorylated neurofilaments. Patterns of immu- noreactivity (linear, flame-shaped, or skein-like within perikarya) greatly resembled the appearance of silver-stained NFT. This pattern of immunoreactivity was not present in hippocampal pyramidal neurons in controls, except in one aged patient in whom adjacent silver-stained sections revealed a few NFT. Patterns of immunoreactivity with antibodies for nonphosphorylated neurofilament proteins were similar in control and AD neurons. Our results indicate that some NFT are associated with abnormal distributions of high molecular weight phosphorylated neurofilament proteins. One domain of the 200-kd protein is believed to be a component of the side arms which link neurofilaments and interact with microtubules. Abnormal interactions of perikaryal neurofilaments could play a role in the genesis of NFT, and this abnormality of the cytoskeleton could contribute to the dysfunction of neurons at risk in AD.",
keywords = "Alzheimer’s disease, Cytoskeleton, Neurofibrillary tangles, Neurofilaments",
author = "Cork, {Linda C.} and Sternberger, {Nancy H.} and Sternberger, {Ludwig A.} and Casanova, {Manuel F.} and Struble, {Robert G.} and Price, {Donald L.}",
year = "1986",
language = "English (US)",
volume = "45",
pages = "56--64",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Phosphorylated neurofilament antigens in neurofibrillary tangles in alzheimer’s disease

AU - Cork, Linda C.

AU - Sternberger, Nancy H.

AU - Sternberger, Ludwig A.

AU - Casanova, Manuel F.

AU - Struble, Robert G.

AU - Price, Donald L.

PY - 1986

Y1 - 1986

N2 - Neurofibrillary tangles (NFT) are a hallmark of Alzheimer’s disease (AD), and their presence correlates with the presence of dementia. A major constituent of NFT is the insoluble paired helical filament which shares some antigenic relationships with normal cytoskeletal elements, particularly neurofilaments. If neurofilament proteins (200, 145-160, and 68 kilodaltons [kd]) participate in the formation of NFT, the distribution of these constituents might be expected to be abnormal. To examine this issue, we used immunocytochemical methods to localize phosphorylated and nonphosphorylated epitopes of neurofilament proteins in hippocampal neurons of controls and patients with AD. Normally, the 200-kd neurofilament protein is not phosphorylated in the perikarya of neurons. However, in AD, many pyramidal neurons contained immunoreactive phosphorylated neurofilaments. Patterns of immu- noreactivity (linear, flame-shaped, or skein-like within perikarya) greatly resembled the appearance of silver-stained NFT. This pattern of immunoreactivity was not present in hippocampal pyramidal neurons in controls, except in one aged patient in whom adjacent silver-stained sections revealed a few NFT. Patterns of immunoreactivity with antibodies for nonphosphorylated neurofilament proteins were similar in control and AD neurons. Our results indicate that some NFT are associated with abnormal distributions of high molecular weight phosphorylated neurofilament proteins. One domain of the 200-kd protein is believed to be a component of the side arms which link neurofilaments and interact with microtubules. Abnormal interactions of perikaryal neurofilaments could play a role in the genesis of NFT, and this abnormality of the cytoskeleton could contribute to the dysfunction of neurons at risk in AD.

AB - Neurofibrillary tangles (NFT) are a hallmark of Alzheimer’s disease (AD), and their presence correlates with the presence of dementia. A major constituent of NFT is the insoluble paired helical filament which shares some antigenic relationships with normal cytoskeletal elements, particularly neurofilaments. If neurofilament proteins (200, 145-160, and 68 kilodaltons [kd]) participate in the formation of NFT, the distribution of these constituents might be expected to be abnormal. To examine this issue, we used immunocytochemical methods to localize phosphorylated and nonphosphorylated epitopes of neurofilament proteins in hippocampal neurons of controls and patients with AD. Normally, the 200-kd neurofilament protein is not phosphorylated in the perikarya of neurons. However, in AD, many pyramidal neurons contained immunoreactive phosphorylated neurofilaments. Patterns of immu- noreactivity (linear, flame-shaped, or skein-like within perikarya) greatly resembled the appearance of silver-stained NFT. This pattern of immunoreactivity was not present in hippocampal pyramidal neurons in controls, except in one aged patient in whom adjacent silver-stained sections revealed a few NFT. Patterns of immunoreactivity with antibodies for nonphosphorylated neurofilament proteins were similar in control and AD neurons. Our results indicate that some NFT are associated with abnormal distributions of high molecular weight phosphorylated neurofilament proteins. One domain of the 200-kd protein is believed to be a component of the side arms which link neurofilaments and interact with microtubules. Abnormal interactions of perikaryal neurofilaments could play a role in the genesis of NFT, and this abnormality of the cytoskeleton could contribute to the dysfunction of neurons at risk in AD.

KW - Alzheimer’s disease

KW - Cytoskeleton

KW - Neurofibrillary tangles

KW - Neurofilaments

UR - http://www.scopus.com/inward/record.url?scp=0022643225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022643225&partnerID=8YFLogxK

M3 - Article

C2 - 3510274

AN - SCOPUS:0022643225

VL - 45

SP - 56

EP - 64

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 1

ER -