Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer's disease

J. C. Vickers, B. M. Riederer, R. A. Marugg, V. Buée-Scherrer, L. Buée, A. Delacourte, John Morrison

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The distribution of immunoreactivity for the neurofilament triplet class of intermediate filament proteins was examined in the hippocampus of young, adult and elderly control cases and compared to that of Alzheimer's disease cases. In a similar fashion to non-human mammalian species, pyramidal neurons in the CA1 region showed a very low degree of neurofilament triplet immunoreactivity in the three younger control cases examined. However, in the other control cases of 49 years of age and older, many CA1 pyramidal neurons showed elevated neurofilament immunoreactivity. In the Alzheimer's disease cases, most of the surviving CA1 neurons showed intense labeling for the neurofilament triplet proteins, with many of these neurons giving off abnormal "sprouting" processes. Double labeling demonstrated that many of these neurons contained tangle-like or granular material that was immunoreactive for abnormal forms of tau and stained with thioflavine S, indicating that these neurons are in a transitional degenerative stage. An antibody to phosphorylated neurofilament proteins labeled a subset of neurofibrillary tangles in the Alzheimer's disease cases. However, following formic acid pre-treatment, the number of neurofibrillary tangles showing phosphorylated neurofilament protein immunoreactivity increased, with double labeling confirming that all of the tau-immunoreactive neurofibrillary tangles were also immunoreactive for phosphorylated neurofilament proteins. Immunoblotting demonstrated that there was a proportionately greater amount of the neurofilament triplet subunit proteins in hippocampal tissue from Alzheimer's disease cases as compared to controls. These results indicate that there are changes in the cytoskeleton of CA1 neurons associated with age which are likely to involve an increase in the level of neurofilament proteins and may be a predisposing factor contributing towards their high degree of vulnerability in degenerative conditions such as Alzheimer's disease. The cellular factors affecting hippocampal neurons during aging may be potentiated in Alzheimer's disease to result in even higher levels of intracellular neurofilament proteins and the progressive alterations of neurofilaments and other cytoskeletal proteins that finally results in neurofibrillary tangle formation and cellular degeneration.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalNeuroscience
Volume62
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Neurofilament Proteins
Alzheimer Disease
Neurofibrillary Tangles
Intermediate Filaments
Neurons
formic acid
Pyramidal Cells
Intermediate Filament Proteins
Cytoskeletal Proteins
Cytoskeleton
Immunoblotting
Causality
Young Adult
Hippocampus
Antibodies

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer's disease. / Vickers, J. C.; Riederer, B. M.; Marugg, R. A.; Buée-Scherrer, V.; Buée, L.; Delacourte, A.; Morrison, John.

In: Neuroscience, Vol. 62, No. 1, 01.01.1994, p. 1-13.

Research output: Contribution to journalArticle

Vickers, J. C. ; Riederer, B. M. ; Marugg, R. A. ; Buée-Scherrer, V. ; Buée, L. ; Delacourte, A. ; Morrison, John. / Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer's disease. In: Neuroscience. 1994 ; Vol. 62, No. 1. pp. 1-13.
@article{825abf28ec744cc1928c0630eb4c7773,
title = "Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer's disease",
abstract = "The distribution of immunoreactivity for the neurofilament triplet class of intermediate filament proteins was examined in the hippocampus of young, adult and elderly control cases and compared to that of Alzheimer's disease cases. In a similar fashion to non-human mammalian species, pyramidal neurons in the CA1 region showed a very low degree of neurofilament triplet immunoreactivity in the three younger control cases examined. However, in the other control cases of 49 years of age and older, many CA1 pyramidal neurons showed elevated neurofilament immunoreactivity. In the Alzheimer's disease cases, most of the surviving CA1 neurons showed intense labeling for the neurofilament triplet proteins, with many of these neurons giving off abnormal {"}sprouting{"} processes. Double labeling demonstrated that many of these neurons contained tangle-like or granular material that was immunoreactive for abnormal forms of tau and stained with thioflavine S, indicating that these neurons are in a transitional degenerative stage. An antibody to phosphorylated neurofilament proteins labeled a subset of neurofibrillary tangles in the Alzheimer's disease cases. However, following formic acid pre-treatment, the number of neurofibrillary tangles showing phosphorylated neurofilament protein immunoreactivity increased, with double labeling confirming that all of the tau-immunoreactive neurofibrillary tangles were also immunoreactive for phosphorylated neurofilament proteins. Immunoblotting demonstrated that there was a proportionately greater amount of the neurofilament triplet subunit proteins in hippocampal tissue from Alzheimer's disease cases as compared to controls. These results indicate that there are changes in the cytoskeleton of CA1 neurons associated with age which are likely to involve an increase in the level of neurofilament proteins and may be a predisposing factor contributing towards their high degree of vulnerability in degenerative conditions such as Alzheimer's disease. The cellular factors affecting hippocampal neurons during aging may be potentiated in Alzheimer's disease to result in even higher levels of intracellular neurofilament proteins and the progressive alterations of neurofilaments and other cytoskeletal proteins that finally results in neurofibrillary tangle formation and cellular degeneration.",
author = "Vickers, {J. C.} and Riederer, {B. M.} and Marugg, {R. A.} and V. Bu{\'e}e-Scherrer and L. Bu{\'e}e and A. Delacourte and John Morrison",
year = "1994",
month = "1",
day = "1",
doi = "10.1016/0306-4522(94)90310-7",
language = "English (US)",
volume = "62",
pages = "1--13",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer's disease

AU - Vickers, J. C.

AU - Riederer, B. M.

AU - Marugg, R. A.

AU - Buée-Scherrer, V.

AU - Buée, L.

AU - Delacourte, A.

AU - Morrison, John

PY - 1994/1/1

Y1 - 1994/1/1

N2 - The distribution of immunoreactivity for the neurofilament triplet class of intermediate filament proteins was examined in the hippocampus of young, adult and elderly control cases and compared to that of Alzheimer's disease cases. In a similar fashion to non-human mammalian species, pyramidal neurons in the CA1 region showed a very low degree of neurofilament triplet immunoreactivity in the three younger control cases examined. However, in the other control cases of 49 years of age and older, many CA1 pyramidal neurons showed elevated neurofilament immunoreactivity. In the Alzheimer's disease cases, most of the surviving CA1 neurons showed intense labeling for the neurofilament triplet proteins, with many of these neurons giving off abnormal "sprouting" processes. Double labeling demonstrated that many of these neurons contained tangle-like or granular material that was immunoreactive for abnormal forms of tau and stained with thioflavine S, indicating that these neurons are in a transitional degenerative stage. An antibody to phosphorylated neurofilament proteins labeled a subset of neurofibrillary tangles in the Alzheimer's disease cases. However, following formic acid pre-treatment, the number of neurofibrillary tangles showing phosphorylated neurofilament protein immunoreactivity increased, with double labeling confirming that all of the tau-immunoreactive neurofibrillary tangles were also immunoreactive for phosphorylated neurofilament proteins. Immunoblotting demonstrated that there was a proportionately greater amount of the neurofilament triplet subunit proteins in hippocampal tissue from Alzheimer's disease cases as compared to controls. These results indicate that there are changes in the cytoskeleton of CA1 neurons associated with age which are likely to involve an increase in the level of neurofilament proteins and may be a predisposing factor contributing towards their high degree of vulnerability in degenerative conditions such as Alzheimer's disease. The cellular factors affecting hippocampal neurons during aging may be potentiated in Alzheimer's disease to result in even higher levels of intracellular neurofilament proteins and the progressive alterations of neurofilaments and other cytoskeletal proteins that finally results in neurofibrillary tangle formation and cellular degeneration.

AB - The distribution of immunoreactivity for the neurofilament triplet class of intermediate filament proteins was examined in the hippocampus of young, adult and elderly control cases and compared to that of Alzheimer's disease cases. In a similar fashion to non-human mammalian species, pyramidal neurons in the CA1 region showed a very low degree of neurofilament triplet immunoreactivity in the three younger control cases examined. However, in the other control cases of 49 years of age and older, many CA1 pyramidal neurons showed elevated neurofilament immunoreactivity. In the Alzheimer's disease cases, most of the surviving CA1 neurons showed intense labeling for the neurofilament triplet proteins, with many of these neurons giving off abnormal "sprouting" processes. Double labeling demonstrated that many of these neurons contained tangle-like or granular material that was immunoreactive for abnormal forms of tau and stained with thioflavine S, indicating that these neurons are in a transitional degenerative stage. An antibody to phosphorylated neurofilament proteins labeled a subset of neurofibrillary tangles in the Alzheimer's disease cases. However, following formic acid pre-treatment, the number of neurofibrillary tangles showing phosphorylated neurofilament protein immunoreactivity increased, with double labeling confirming that all of the tau-immunoreactive neurofibrillary tangles were also immunoreactive for phosphorylated neurofilament proteins. Immunoblotting demonstrated that there was a proportionately greater amount of the neurofilament triplet subunit proteins in hippocampal tissue from Alzheimer's disease cases as compared to controls. These results indicate that there are changes in the cytoskeleton of CA1 neurons associated with age which are likely to involve an increase in the level of neurofilament proteins and may be a predisposing factor contributing towards their high degree of vulnerability in degenerative conditions such as Alzheimer's disease. The cellular factors affecting hippocampal neurons during aging may be potentiated in Alzheimer's disease to result in even higher levels of intracellular neurofilament proteins and the progressive alterations of neurofilaments and other cytoskeletal proteins that finally results in neurofibrillary tangle formation and cellular degeneration.

UR - http://www.scopus.com/inward/record.url?scp=0028101798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028101798&partnerID=8YFLogxK

U2 - 10.1016/0306-4522(94)90310-7

DO - 10.1016/0306-4522(94)90310-7

M3 - Article

C2 - 7816192

AN - SCOPUS:0028101798

VL - 62

SP - 1

EP - 13

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 1

ER -