Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease

I. Superior frontal and inferior temporal cortex

Patrick R. Hof, John Morrison, Kevin Cox

Research output: Contribution to journalArticle

279 Citations (Scopus)

Abstract

Various cytoskeletal proteins have been implicated in the cellular pathology of Alzheimer's disease. A monoclonal antibody (SMI32) that recognizes nonphosphorylated epitopes on the medium (168 kDa) and heavy (200 kDa) subunits of neurofilament proteins has been used to label and analyze a specific subpopulation of pyramidal neurons in the prefrontal and inferior temporal cortices of normal and Alzheimer's disease brains. In Alzheimer's disease, the distribution of neuropathological markers predominates in layers III and V in these association areas. In these neocortical regions, SMI32 primarily labels the perikarya and dendrites of large pyramidal neurons, predominantly located within layers III and V. In Alzheimer's disease, a dramatic loss of SMI32‐immunoreactive (ir) cells was observed, affecting particularly the largest cells (i.e., cells with a cross‐sectional perikaryal area larger than 350 m̈m2). The staining intensity of the largest SMI32‐ir neurons was significantly reduced in Alzheimer's disease cases, suggesting that an inappropriate phosphorylation of these cytoskeletal proteins may take place in the course of the pathological process. In addition, the SMI32‐ir neuron loss and total neuron loss were highly correlated with neurofibrillary tangle counts, whereas such a correlation was not observed with neuritic plaque counts. These quantitative data suggest that SMI32‐ir neurons represent a small subset of pyramidal cells that share certain anatomical and molecular characteristics and are highly vulnerable in Alzheimer's disease. Other studies have suggested that SMI32‐ir neurons are likely to furnish long corticocortical projections. Thus, their loss would substantially diminish the effectiveness of the distributed processing capacity of the neocortex, resulting in a neocortical isolation syndrome as reflected by the clinical symptomatology observed in these patients. Such correlations between the expression of a selective cellular pathology and specific elements of cortical circuitry will increase our understanding of the molecular and cellular characteristics underlying a given neuronal subclass vulnerability in Alzheimer's disease or other neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)44-54
Number of pages11
JournalJournal of Comparative Neurology
Volume301
Issue number1
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

Fingerprint

Pyramidal Cells
Temporal Lobe
Alzheimer Disease
Neurons
Cytoskeletal Proteins
Pathology
Neurofilament Proteins
Neurofibrillary Tangles
Neocortex
Amyloid Plaques
Pathologic Processes
Dendrites
Neurodegenerative Diseases
Epitopes
Monoclonal Antibodies
Phosphorylation
Staining and Labeling
Brain

Keywords

  • association cortex
  • corticocortical connections
  • human brain
  • neurodegenerative disorders
  • neurofilament proteins
  • quantitative neuroanatomy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease : I. Superior frontal and inferior temporal cortex. / Hof, Patrick R.; Morrison, John; Cox, Kevin.

In: Journal of Comparative Neurology, Vol. 301, No. 1, 01.01.1990, p. 44-54.

Research output: Contribution to journalArticle

@article{fa45ccd843ab4f9ca7fd228b989e6b14,
title = "Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: I. Superior frontal and inferior temporal cortex",
abstract = "Various cytoskeletal proteins have been implicated in the cellular pathology of Alzheimer's disease. A monoclonal antibody (SMI32) that recognizes nonphosphorylated epitopes on the medium (168 kDa) and heavy (200 kDa) subunits of neurofilament proteins has been used to label and analyze a specific subpopulation of pyramidal neurons in the prefrontal and inferior temporal cortices of normal and Alzheimer's disease brains. In Alzheimer's disease, the distribution of neuropathological markers predominates in layers III and V in these association areas. In these neocortical regions, SMI32 primarily labels the perikarya and dendrites of large pyramidal neurons, predominantly located within layers III and V. In Alzheimer's disease, a dramatic loss of SMI32‐immunoreactive (ir) cells was observed, affecting particularly the largest cells (i.e., cells with a cross‐sectional perikaryal area larger than 350 m̈m2). The staining intensity of the largest SMI32‐ir neurons was significantly reduced in Alzheimer's disease cases, suggesting that an inappropriate phosphorylation of these cytoskeletal proteins may take place in the course of the pathological process. In addition, the SMI32‐ir neuron loss and total neuron loss were highly correlated with neurofibrillary tangle counts, whereas such a correlation was not observed with neuritic plaque counts. These quantitative data suggest that SMI32‐ir neurons represent a small subset of pyramidal cells that share certain anatomical and molecular characteristics and are highly vulnerable in Alzheimer's disease. Other studies have suggested that SMI32‐ir neurons are likely to furnish long corticocortical projections. Thus, their loss would substantially diminish the effectiveness of the distributed processing capacity of the neocortex, resulting in a neocortical isolation syndrome as reflected by the clinical symptomatology observed in these patients. Such correlations between the expression of a selective cellular pathology and specific elements of cortical circuitry will increase our understanding of the molecular and cellular characteristics underlying a given neuronal subclass vulnerability in Alzheimer's disease or other neurodegenerative disorders.",
keywords = "association cortex, corticocortical connections, human brain, neurodegenerative disorders, neurofilament proteins, quantitative neuroanatomy",
author = "Hof, {Patrick R.} and John Morrison and Kevin Cox",
year = "1990",
month = "1",
day = "1",
doi = "10.1002/cne.903010105",
language = "English (US)",
volume = "301",
pages = "44--54",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease

T2 - I. Superior frontal and inferior temporal cortex

AU - Hof, Patrick R.

AU - Morrison, John

AU - Cox, Kevin

PY - 1990/1/1

Y1 - 1990/1/1

N2 - Various cytoskeletal proteins have been implicated in the cellular pathology of Alzheimer's disease. A monoclonal antibody (SMI32) that recognizes nonphosphorylated epitopes on the medium (168 kDa) and heavy (200 kDa) subunits of neurofilament proteins has been used to label and analyze a specific subpopulation of pyramidal neurons in the prefrontal and inferior temporal cortices of normal and Alzheimer's disease brains. In Alzheimer's disease, the distribution of neuropathological markers predominates in layers III and V in these association areas. In these neocortical regions, SMI32 primarily labels the perikarya and dendrites of large pyramidal neurons, predominantly located within layers III and V. In Alzheimer's disease, a dramatic loss of SMI32‐immunoreactive (ir) cells was observed, affecting particularly the largest cells (i.e., cells with a cross‐sectional perikaryal area larger than 350 m̈m2). The staining intensity of the largest SMI32‐ir neurons was significantly reduced in Alzheimer's disease cases, suggesting that an inappropriate phosphorylation of these cytoskeletal proteins may take place in the course of the pathological process. In addition, the SMI32‐ir neuron loss and total neuron loss were highly correlated with neurofibrillary tangle counts, whereas such a correlation was not observed with neuritic plaque counts. These quantitative data suggest that SMI32‐ir neurons represent a small subset of pyramidal cells that share certain anatomical and molecular characteristics and are highly vulnerable in Alzheimer's disease. Other studies have suggested that SMI32‐ir neurons are likely to furnish long corticocortical projections. Thus, their loss would substantially diminish the effectiveness of the distributed processing capacity of the neocortex, resulting in a neocortical isolation syndrome as reflected by the clinical symptomatology observed in these patients. Such correlations between the expression of a selective cellular pathology and specific elements of cortical circuitry will increase our understanding of the molecular and cellular characteristics underlying a given neuronal subclass vulnerability in Alzheimer's disease or other neurodegenerative disorders.

AB - Various cytoskeletal proteins have been implicated in the cellular pathology of Alzheimer's disease. A monoclonal antibody (SMI32) that recognizes nonphosphorylated epitopes on the medium (168 kDa) and heavy (200 kDa) subunits of neurofilament proteins has been used to label and analyze a specific subpopulation of pyramidal neurons in the prefrontal and inferior temporal cortices of normal and Alzheimer's disease brains. In Alzheimer's disease, the distribution of neuropathological markers predominates in layers III and V in these association areas. In these neocortical regions, SMI32 primarily labels the perikarya and dendrites of large pyramidal neurons, predominantly located within layers III and V. In Alzheimer's disease, a dramatic loss of SMI32‐immunoreactive (ir) cells was observed, affecting particularly the largest cells (i.e., cells with a cross‐sectional perikaryal area larger than 350 m̈m2). The staining intensity of the largest SMI32‐ir neurons was significantly reduced in Alzheimer's disease cases, suggesting that an inappropriate phosphorylation of these cytoskeletal proteins may take place in the course of the pathological process. In addition, the SMI32‐ir neuron loss and total neuron loss were highly correlated with neurofibrillary tangle counts, whereas such a correlation was not observed with neuritic plaque counts. These quantitative data suggest that SMI32‐ir neurons represent a small subset of pyramidal cells that share certain anatomical and molecular characteristics and are highly vulnerable in Alzheimer's disease. Other studies have suggested that SMI32‐ir neurons are likely to furnish long corticocortical projections. Thus, their loss would substantially diminish the effectiveness of the distributed processing capacity of the neocortex, resulting in a neocortical isolation syndrome as reflected by the clinical symptomatology observed in these patients. Such correlations between the expression of a selective cellular pathology and specific elements of cortical circuitry will increase our understanding of the molecular and cellular characteristics underlying a given neuronal subclass vulnerability in Alzheimer's disease or other neurodegenerative disorders.

KW - association cortex

KW - corticocortical connections

KW - human brain

KW - neurodegenerative disorders

KW - neurofilament proteins

KW - quantitative neuroanatomy

UR - http://www.scopus.com/inward/record.url?scp=0025036899&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025036899&partnerID=8YFLogxK

U2 - 10.1002/cne.903010105

DO - 10.1002/cne.903010105

M3 - Article

VL - 301

SP - 44

EP - 54

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

IS - 1

ER -