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 language | English (US) |
|---|---|
| Pages (from-to) | 56-64 |
| Number of pages | 9 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 45 |
| Issue number | 1 |
| State | Published - 1986 |
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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
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 journal › Article
}
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 -