Non-plaque dystrophic dendrites in Alzheimer hippocampus: A new pathological structure revealed by glutamate receptor immunocytochemistry

E. Aronica, D. W. Dickson, Y. Kress, John Morrison, R. S. Zukin

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Alzheimer's disease is a progressive dementia characterized by a pronounced neurodegeneration in the entorhinal cortex, hippocampal CA1, and subiculum. Excitatory amino acid receptor-mediated excitotoxicity is postulated to play a role in the neurodegeneration in Alzheimer's disease. The present study investigated immunocytochemical localization of excitatory amino acid receptor subunits in the hippocampus of twelve Alzheimer's disease and eleven controls, matched for age, sex and post mortem interval. Immunocytochemistry with antibodies specific for glutamate receptors GluR1, GluR2(4) (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), GluR5/6/7 (kainate) and NRI (N-methyl-D-aspartate) receptor subunits demonstrated that virtually all projection neurons in all subfields contained subunits from each receptor class. However, regional differences in immunoreactivity were apparent in Alzheimer's disease vs normal human brain. In the vulnerable due to cell loss. In contrast, GluR2(4) immunolabelling appeared to be increased in the inner portion of the molecular layer of the dentate gyrus. In addition to cellular labelling, GluR1, GluR2(4) and NR1 immunolabelling revealed a novel pathological structure in 12 of 12 Alzheimer's disease, but none of the control brains. The lesions were juxtacellular clusters of granular immunoreactivity in the neuropil of the pyramidal cell layer. Ultrastructural analysis revealed these to be cellular processes containing dense vesicles and flocculent material with immunolabelling localized to plasma and vesicular membranes. They were not specifically associated with amyloid fibrils and did not contain paired helical filaments and they were also distinct from granulovacuolar degeneration. Several structures contained Hirano body filaments indicating that the dystrophic processes were most likely dendritic in origin. Additional studies are needed to determine the pathogenesis of these lesions, which could provide an additional index of dendritic deterioration in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)979-991
Number of pages13
JournalNeuroscience
Volume82
Issue number4
DOIs
StatePublished - Nov 12 1997
Externally publishedYes

Fingerprint

Glutamate Receptors
Dendrites
Hippocampus
Alzheimer Disease
Immunohistochemistry
Entorhinal Cortex
Neuropil
Pyramidal Cells
Kainic Acid
Dentate Gyrus
Brain
N-Methyl-D-Aspartate Receptors
Amyloid
Dementia
Cell Membrane
Neurons
Antibodies

Keywords

  • Alzheimer's diseases
  • Glutamate receptors
  • Hippocampus
  • Immunocytochemistry
  • Non-plaque dystrophic dendrites

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Non-plaque dystrophic dendrites in Alzheimer hippocampus : A new pathological structure revealed by glutamate receptor immunocytochemistry. / Aronica, E.; Dickson, D. W.; Kress, Y.; Morrison, John; Zukin, R. S.

In: Neuroscience, Vol. 82, No. 4, 12.11.1997, p. 979-991.

Research output: Contribution to journalArticle

@article{5b8133d60904445ba09391eb2dbc91e2,
title = "Non-plaque dystrophic dendrites in Alzheimer hippocampus: A new pathological structure revealed by glutamate receptor immunocytochemistry",
abstract = "Alzheimer's disease is a progressive dementia characterized by a pronounced neurodegeneration in the entorhinal cortex, hippocampal CA1, and subiculum. Excitatory amino acid receptor-mediated excitotoxicity is postulated to play a role in the neurodegeneration in Alzheimer's disease. The present study investigated immunocytochemical localization of excitatory amino acid receptor subunits in the hippocampus of twelve Alzheimer's disease and eleven controls, matched for age, sex and post mortem interval. Immunocytochemistry with antibodies specific for glutamate receptors GluR1, GluR2(4) (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), GluR5/6/7 (kainate) and NRI (N-methyl-D-aspartate) receptor subunits demonstrated that virtually all projection neurons in all subfields contained subunits from each receptor class. However, regional differences in immunoreactivity were apparent in Alzheimer's disease vs normal human brain. In the vulnerable due to cell loss. In contrast, GluR2(4) immunolabelling appeared to be increased in the inner portion of the molecular layer of the dentate gyrus. In addition to cellular labelling, GluR1, GluR2(4) and NR1 immunolabelling revealed a novel pathological structure in 12 of 12 Alzheimer's disease, but none of the control brains. The lesions were juxtacellular clusters of granular immunoreactivity in the neuropil of the pyramidal cell layer. Ultrastructural analysis revealed these to be cellular processes containing dense vesicles and flocculent material with immunolabelling localized to plasma and vesicular membranes. They were not specifically associated with amyloid fibrils and did not contain paired helical filaments and they were also distinct from granulovacuolar degeneration. Several structures contained Hirano body filaments indicating that the dystrophic processes were most likely dendritic in origin. Additional studies are needed to determine the pathogenesis of these lesions, which could provide an additional index of dendritic deterioration in Alzheimer's disease.",
keywords = "Alzheimer's diseases, Glutamate receptors, Hippocampus, Immunocytochemistry, Non-plaque dystrophic dendrites",
author = "E. Aronica and Dickson, {D. W.} and Y. Kress and John Morrison and Zukin, {R. S.}",
year = "1997",
month = "11",
day = "12",
doi = "10.1016/S0306-4522(97)00260-1",
language = "English (US)",
volume = "82",
pages = "979--991",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - Non-plaque dystrophic dendrites in Alzheimer hippocampus

T2 - A new pathological structure revealed by glutamate receptor immunocytochemistry

AU - Aronica, E.

AU - Dickson, D. W.

AU - Kress, Y.

AU - Morrison, John

AU - Zukin, R. S.

PY - 1997/11/12

Y1 - 1997/11/12

N2 - Alzheimer's disease is a progressive dementia characterized by a pronounced neurodegeneration in the entorhinal cortex, hippocampal CA1, and subiculum. Excitatory amino acid receptor-mediated excitotoxicity is postulated to play a role in the neurodegeneration in Alzheimer's disease. The present study investigated immunocytochemical localization of excitatory amino acid receptor subunits in the hippocampus of twelve Alzheimer's disease and eleven controls, matched for age, sex and post mortem interval. Immunocytochemistry with antibodies specific for glutamate receptors GluR1, GluR2(4) (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), GluR5/6/7 (kainate) and NRI (N-methyl-D-aspartate) receptor subunits demonstrated that virtually all projection neurons in all subfields contained subunits from each receptor class. However, regional differences in immunoreactivity were apparent in Alzheimer's disease vs normal human brain. In the vulnerable due to cell loss. In contrast, GluR2(4) immunolabelling appeared to be increased in the inner portion of the molecular layer of the dentate gyrus. In addition to cellular labelling, GluR1, GluR2(4) and NR1 immunolabelling revealed a novel pathological structure in 12 of 12 Alzheimer's disease, but none of the control brains. The lesions were juxtacellular clusters of granular immunoreactivity in the neuropil of the pyramidal cell layer. Ultrastructural analysis revealed these to be cellular processes containing dense vesicles and flocculent material with immunolabelling localized to plasma and vesicular membranes. They were not specifically associated with amyloid fibrils and did not contain paired helical filaments and they were also distinct from granulovacuolar degeneration. Several structures contained Hirano body filaments indicating that the dystrophic processes were most likely dendritic in origin. Additional studies are needed to determine the pathogenesis of these lesions, which could provide an additional index of dendritic deterioration in Alzheimer's disease.

AB - Alzheimer's disease is a progressive dementia characterized by a pronounced neurodegeneration in the entorhinal cortex, hippocampal CA1, and subiculum. Excitatory amino acid receptor-mediated excitotoxicity is postulated to play a role in the neurodegeneration in Alzheimer's disease. The present study investigated immunocytochemical localization of excitatory amino acid receptor subunits in the hippocampus of twelve Alzheimer's disease and eleven controls, matched for age, sex and post mortem interval. Immunocytochemistry with antibodies specific for glutamate receptors GluR1, GluR2(4) (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), GluR5/6/7 (kainate) and NRI (N-methyl-D-aspartate) receptor subunits demonstrated that virtually all projection neurons in all subfields contained subunits from each receptor class. However, regional differences in immunoreactivity were apparent in Alzheimer's disease vs normal human brain. In the vulnerable due to cell loss. In contrast, GluR2(4) immunolabelling appeared to be increased in the inner portion of the molecular layer of the dentate gyrus. In addition to cellular labelling, GluR1, GluR2(4) and NR1 immunolabelling revealed a novel pathological structure in 12 of 12 Alzheimer's disease, but none of the control brains. The lesions were juxtacellular clusters of granular immunoreactivity in the neuropil of the pyramidal cell layer. Ultrastructural analysis revealed these to be cellular processes containing dense vesicles and flocculent material with immunolabelling localized to plasma and vesicular membranes. They were not specifically associated with amyloid fibrils and did not contain paired helical filaments and they were also distinct from granulovacuolar degeneration. Several structures contained Hirano body filaments indicating that the dystrophic processes were most likely dendritic in origin. Additional studies are needed to determine the pathogenesis of these lesions, which could provide an additional index of dendritic deterioration in Alzheimer's disease.

KW - Alzheimer's diseases

KW - Glutamate receptors

KW - Hippocampus

KW - Immunocytochemistry

KW - Non-plaque dystrophic dendrites

UR - http://www.scopus.com/inward/record.url?scp=0342617716&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342617716&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(97)00260-1

DO - 10.1016/S0306-4522(97)00260-1

M3 - Article

C2 - 9466422

AN - SCOPUS:0342617716

VL - 82

SP - 979

EP - 991

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 4

ER -