The genesis of the senile plaque: Further evidence in support of its neuronal origin

Miguel Pappolla, R. A. Omar, K. Sambamurti, J. P. Anderson, N. K. Robakis

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Senile plaques are among the most conspicuous neuropathologic changes found in the brains of elderly individuals and patients with Alzheimer's disease (AD). The origin of the amyloid beta protein (AβP) that accumulates in senile plaques continues to be highly controversial. Recently, using quantitative immunohistochemistry and computerized image analysis, we obtained evidence that at least a subset of early ("diffuse") senile plaques originate from neurons. In the current investigation, we employed monoclonal antibodies to AβP and the same computerized methodology to examine in further detail the quantitative patterns of AβP deposition in diffuse plaques in a population of intellectually intact elderly individuals. The presence of neurocentric concentration gradients of AβP accumulation was confirmed in this study. Most significantly, this was the most predominant pattern of early amyloid deposition in the population studied. The highest concentration of AβP was centered around neuronal cell bodies or their processes, and occasionally along neuronal plasma membranes. Computerized images showed patterns that can be interpreted as a pathogenetic sequence ranging from initial neurogenic concentration gradients centered around one single neuron to larger deposits (diffuse plaques) composed of several "anastomosing" gradients involving several adjacent neurons. It is proposed that the described very early deposits constitute the initial stage in the development of the senile plaque. Although this study does not fully prove that the accumulated AβP is synthesized in the neuron or neuronal process it surrounds, the images herein presented suggest that neurons are the initial nidus of plaque formation.

Original languageEnglish (US)
Pages (from-to)1151-1159
Number of pages9
JournalAmerican Journal of Pathology
Volume141
Issue number5
StatePublished - Nov 1992
Externally publishedYes

Fingerprint

Amyloid beta-Peptides
Amyloid Plaques
Neurons
Amyloid
Population
Alzheimer Disease
Immunohistochemistry
Monoclonal Antibodies
Cell Membrane
Brain

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Pappolla, M., Omar, R. A., Sambamurti, K., Anderson, J. P., & Robakis, N. K. (1992). The genesis of the senile plaque: Further evidence in support of its neuronal origin. American Journal of Pathology, 141(5), 1151-1159.

The genesis of the senile plaque : Further evidence in support of its neuronal origin. / Pappolla, Miguel; Omar, R. A.; Sambamurti, K.; Anderson, J. P.; Robakis, N. K.

In: American Journal of Pathology, Vol. 141, No. 5, 11.1992, p. 1151-1159.

Research output: Contribution to journalArticle

Pappolla, M, Omar, RA, Sambamurti, K, Anderson, JP & Robakis, NK 1992, 'The genesis of the senile plaque: Further evidence in support of its neuronal origin', American Journal of Pathology, vol. 141, no. 5, pp. 1151-1159.
Pappolla, Miguel ; Omar, R. A. ; Sambamurti, K. ; Anderson, J. P. ; Robakis, N. K. / The genesis of the senile plaque : Further evidence in support of its neuronal origin. In: American Journal of Pathology. 1992 ; Vol. 141, No. 5. pp. 1151-1159.
@article{8980ce6d519a4b96af3706caf0213ce1,
title = "The genesis of the senile plaque: Further evidence in support of its neuronal origin",
abstract = "Senile plaques are among the most conspicuous neuropathologic changes found in the brains of elderly individuals and patients with Alzheimer's disease (AD). The origin of the amyloid beta protein (AβP) that accumulates in senile plaques continues to be highly controversial. Recently, using quantitative immunohistochemistry and computerized image analysis, we obtained evidence that at least a subset of early ({"}diffuse{"}) senile plaques originate from neurons. In the current investigation, we employed monoclonal antibodies to AβP and the same computerized methodology to examine in further detail the quantitative patterns of AβP deposition in diffuse plaques in a population of intellectually intact elderly individuals. The presence of neurocentric concentration gradients of AβP accumulation was confirmed in this study. Most significantly, this was the most predominant pattern of early amyloid deposition in the population studied. The highest concentration of AβP was centered around neuronal cell bodies or their processes, and occasionally along neuronal plasma membranes. Computerized images showed patterns that can be interpreted as a pathogenetic sequence ranging from initial neurogenic concentration gradients centered around one single neuron to larger deposits (diffuse plaques) composed of several {"}anastomosing{"} gradients involving several adjacent neurons. It is proposed that the described very early deposits constitute the initial stage in the development of the senile plaque. Although this study does not fully prove that the accumulated AβP is synthesized in the neuron or neuronal process it surrounds, the images herein presented suggest that neurons are the initial nidus of plaque formation.",
author = "Miguel Pappolla and Omar, {R. A.} and K. Sambamurti and Anderson, {J. P.} and Robakis, {N. K.}",
year = "1992",
month = "11",
language = "English (US)",
volume = "141",
pages = "1151--1159",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - The genesis of the senile plaque

T2 - Further evidence in support of its neuronal origin

AU - Pappolla, Miguel

AU - Omar, R. A.

AU - Sambamurti, K.

AU - Anderson, J. P.

AU - Robakis, N. K.

PY - 1992/11

Y1 - 1992/11

N2 - Senile plaques are among the most conspicuous neuropathologic changes found in the brains of elderly individuals and patients with Alzheimer's disease (AD). The origin of the amyloid beta protein (AβP) that accumulates in senile plaques continues to be highly controversial. Recently, using quantitative immunohistochemistry and computerized image analysis, we obtained evidence that at least a subset of early ("diffuse") senile plaques originate from neurons. In the current investigation, we employed monoclonal antibodies to AβP and the same computerized methodology to examine in further detail the quantitative patterns of AβP deposition in diffuse plaques in a population of intellectually intact elderly individuals. The presence of neurocentric concentration gradients of AβP accumulation was confirmed in this study. Most significantly, this was the most predominant pattern of early amyloid deposition in the population studied. The highest concentration of AβP was centered around neuronal cell bodies or their processes, and occasionally along neuronal plasma membranes. Computerized images showed patterns that can be interpreted as a pathogenetic sequence ranging from initial neurogenic concentration gradients centered around one single neuron to larger deposits (diffuse plaques) composed of several "anastomosing" gradients involving several adjacent neurons. It is proposed that the described very early deposits constitute the initial stage in the development of the senile plaque. Although this study does not fully prove that the accumulated AβP is synthesized in the neuron or neuronal process it surrounds, the images herein presented suggest that neurons are the initial nidus of plaque formation.

AB - Senile plaques are among the most conspicuous neuropathologic changes found in the brains of elderly individuals and patients with Alzheimer's disease (AD). The origin of the amyloid beta protein (AβP) that accumulates in senile plaques continues to be highly controversial. Recently, using quantitative immunohistochemistry and computerized image analysis, we obtained evidence that at least a subset of early ("diffuse") senile plaques originate from neurons. In the current investigation, we employed monoclonal antibodies to AβP and the same computerized methodology to examine in further detail the quantitative patterns of AβP deposition in diffuse plaques in a population of intellectually intact elderly individuals. The presence of neurocentric concentration gradients of AβP accumulation was confirmed in this study. Most significantly, this was the most predominant pattern of early amyloid deposition in the population studied. The highest concentration of AβP was centered around neuronal cell bodies or their processes, and occasionally along neuronal plasma membranes. Computerized images showed patterns that can be interpreted as a pathogenetic sequence ranging from initial neurogenic concentration gradients centered around one single neuron to larger deposits (diffuse plaques) composed of several "anastomosing" gradients involving several adjacent neurons. It is proposed that the described very early deposits constitute the initial stage in the development of the senile plaque. Although this study does not fully prove that the accumulated AβP is synthesized in the neuron or neuronal process it surrounds, the images herein presented suggest that neurons are the initial nidus of plaque formation.

UR - http://www.scopus.com/inward/record.url?scp=0026463731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026463731&partnerID=8YFLogxK

M3 - Article

C2 - 1443049

AN - SCOPUS:0026463731

VL - 141

SP - 1151

EP - 1159

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 5

ER -