Home LiteratureArticle Details
PMID: 8456946 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

An antibody against phosphorylated neurofilaments identifies a subset of damaged association axons in Alzheimer's disease.

The American journal of pathology ·Vol. 142 ·No. 3 ·1993-03-00 ·Pages 871-82

Masliah E, Mallory M, Hansen L, Alford M, DeTeresa R, Terry R

Abstract

We studied axonal damage in Alzheimer's disease frontal cortex and hippocampus with a novel monoclonal antibody (SMI 312) against phosphorylated neurofilaments. This antibody immunolabeled, with great detail, the neuropil axonal network. In aged normal cases only a few pyramidal cell perikarya were immunostained. In Alzheimer's disease there was a two- to four-fold increase in neuronal SMI 312 immunolabeling, and neuropil neuritic processes were severely disrupted. Double-immunolabeling analysis showed that 88% of SMI 312-immunolabeled abnormal neuritic clusters were associated with amyloid, whereas the remaining 12% were not. Serial section analysis and 3-D reconstructions suggested that dystrophic neurites of classical plaques were derived from long axons. These abnormal neurites were also growth-associated protein 43 positive and occasionally tau positive. The present study supports the contention that a subpopulation of aberrantly sprouting axons in the neuritic plaque is derived from cortico-cortico fibers. This disruption of the neocortical association fibers and neuritic microcircuitry could underlie the cognitive impairment of Alzheimer's disease.

MeSH Terms
Aged Aged, 80 and over Alzheimer Disease/metabolism,pathology Antibodies, Monoclonal/immunology Axons/pathology Brain/metabolism,pathology Frontal Lobe/metabolism Hippocampus/metabolism Humans Immunohistochemistry Intermediate Filaments/immunology,metabolism Neurites/metabolism Phosphorylation
Chemicals
Antibodies, Monoclonal
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Masliah E
University of California, San Diego, School of Medicine, Department of Neurosciences, La Jolla.
Mallory M
Hansen L
Alford M
DeTeresa R
Terry R
References (47)
47 references, click to expand
  1. The contribution of altered synapses in the senile plaque: an electron microscopic study in Alzheimer's dementia.
    J Neuropathol Exp Neurol. 1967 Jan;26(1):25-39 PMID: 6022163
  2. ULTRASTRUCTURAL STUDIES IN ALZHEIMER'S PRESENILE DEMENTIA.
    Am J Pathol. 1964 Feb;44:269-97 PMID: 14119171
  3. Some morphometric aspects of the brain in senile dementia of the Alzheimer type.
    Ann Neurol. 1981 Aug;10(2):184-92 PMID: 7283403
  4. Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ.
    Proc Natl Acad Sci U S A. 1983 Oct;80(19):6126-30 PMID: 6577472
  5. Regional cortical dysfunction in Alzheimer's disease as determined by positron emission tomography.
    Ann Neurol. 1984;15 Suppl:S170-4 PMID: 6611118
  6. Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7941-5 PMID: 6083566
  7. Aberrant neurofilament phosphorylation in Alzheimer disease.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4274-6 PMID: 3159022
  8. Immunostaining of neurofilament protein in human postmortem cortex: a sensitive and specific approach to the pattern analysis of human cortical cytoarchitecture.
    Can J Biochem Cell Biol. 1985 Jun;63(6):577-84 PMID: 3930053
  9. Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's disease.
    J Neurosci. 1985 Oct;5(10):2801-8 PMID: 4045553
  10. Phosphorylated neurofilament antigens in neurofibrillary tangles in Alzheimer's disease.
    J Neuropathol Exp Neurol. 1986 Jan;45(1):56-64 PMID: 3510274
  11. Senile plaques in cortex of aged normal monkeys.
    Brain Res. 1985 Dec 30;361(1-2):267-75 PMID: 4084799
  12. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments.
    J Biol Chem. 1986 May 5;261(13):6084-9 PMID: 3084478
  13. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology.
    Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7 PMID: 3088567
  14. Distribution of neurofilament antigens after axonal injury.
    J Neuropathol Exp Neurol. 1987 May;46(3):269-82 PMID: 3549983
  15. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease.
    J Neurol Sci. 1987 Apr;78(2):151-64 PMID: 3572454
  16. Alzheimer dementia: a study of the senile plaque with antisera and a monoclonal antibody specific for neurofilament proteins.
    Acta Histochem Suppl. 1987;34:115-21 PMID: 3107053
  17. Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices.
    J Neurosci. 1987 Jun;7(6):1799-808 PMID: 2439665
  18. Senile plaques in aged squirrel monkeys.
    Neurobiol Aging. 1987 Jul-Aug;8(4):291-6 PMID: 3306432
  19. Tau epitopes are incorporated into a range of lesions in Alzheimer's disease.
    J Neuropathol Exp Neurol. 1987 Nov;46(6):611-22 PMID: 2443617
  20. Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease.
    Ann Neurol. 1987 Nov;22(5):639-43 PMID: 3122646
  21. Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques.
    Am J Pathol. 1988 Jul;132(1):86-101 PMID: 2456021
  22. Expression of neurofilament proteins by Purkinje cells: ultrastructural immunolocalization with monoclonal antibodies.
    Brain Res. 1988 Aug 2;457(1):12-20 PMID: 2458799
  23. Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles.
    J Neuropathol Exp Neurol. 1988 Nov;47(6):654-63 PMID: 2459316
  24. Protein kinase C substrates from bovine brain. Purification and characterization of neuromodulin, a neuron-specific calmodulin-binding protein.
    J Biol Chem. 1989 Jan 25;264(3):1824-8 PMID: 2521487
  25. Synaptic loss in Alzheimer's disease and other dementias.
    Neurology. 1989 Mar;39(3):355-61 PMID: 2927643
  26. Early and late appearance of neurofilament phosphorylation events in nerve regeneration.
    Brain Res Bull. 1989 Feb;22(2):225-32 PMID: 2495845
  27. Amyloid beta-protein deposition in tissues other than brain in Alzheimer's disease.
    Nature. 1989 Sep 21;341(6239):226-30 PMID: 2528696
  28. Microtubular reorganization and dendritic growth response in Alzheimer's disease.
    Ann Neurol. 1989 Nov;26(5):652-9 PMID: 2817839
  29. Defined neurofilament, tau, and beta-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques.
    Proc Natl Acad Sci U S A. 1990 Mar;87(6):2249-53 PMID: 1690426
  30. Quantitative assessment of cortical synaptic density in Alzheimer's disease.
    Neurobiol Aging. 1990 Jan-Feb;11(1):29-37 PMID: 2325814
  31. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity.
    Ann Neurol. 1990 May;27(5):457-64 PMID: 2360787
  32. Diffuse plaques do not accentuate synapse loss in Alzheimer's disease.
    Am J Pathol. 1990 Dec;137(6):1293-7 PMID: 2124413
  33. Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits.
    Am J Pathol. 1990 Dec;137(6):1383-92 PMID: 1701963
  34. Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease.
    Am J Pathol. 1991 Jan;138(1):235-46 PMID: 1899001
  35. Comparative epitope analysis of neuronal cytoskeletal proteins in Alzheimer's disease senile plaque neurites and neuropil threads.
    Lab Invest. 1991 Mar;64(3):352-7 PMID: 1706004
  36. Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: I. Superior frontal and inferior temporal cortex.
    J Comp Neurol. 1990 Nov 1;301(1):44-54 PMID: 2127598
  37. The cytoarchitectonic distribution of senile plaques in three aged monkeys.
    Acta Neuropathol. 1990;81(1):60-5 PMID: 1707575
  38. Patterns of aberrant sprouting in Alzheimer's disease.
    Neuron. 1991 May;6(5):729-39 PMID: 1827266
  39. Immunoelectron microscopic study of synaptic pathology in Alzheimer's disease.
    Acta Neuropathol. 1991;81(4):428-33 PMID: 1903014
  40. Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.
    Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7552-6 PMID: 1652752
  41. Neuritic pathology and dementia in Alzheimer's disease.
    Ann Neurol. 1991 Aug;30(2):156-65 PMID: 1910274
  42. The axonal origin of a subpopulation of dystrophic neurites in Alzheimer's disease.
    Neurosci Lett. 1991 Aug 5;129(1):11-6 PMID: 1922959
  43. Evidence for axonal loss in regions occupied by senile plaques in Alzheimer cortex.
    Neuroscience. 1991;42(3):651-60 PMID: 1956514
  44. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
    Ann Neurol. 1991 Oct;30(4):572-80 PMID: 1789684
  45. Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease.
    J Neuropathol Exp Neurol. 1992 Jul;51(4):404-14 PMID: 1619440
  46. Localization of amyloid precursor protein in GAP43-immunoreactive aberrant sprouting neurites in Alzheimer's disease.
    Brain Res. 1992 Mar 6;574(1-2):312-6 PMID: 1386275
  47. Pathologic axons and synapses in human neuropsychiatric disorders.
    Hum Pathol. 1975 Sep;6(5):571-82 PMID: 170188
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1993-03-00
Pages
871-82
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1886791
Subset
IM
Grants
NIA NIH HHS · AG05131 · United States
NIA NIH HHS · AG08201 · United States
NIA NIH HHS · AG08205 · United States
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2