Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer’s disease

T. Bussière, P. D. Friend, N. Sadeghi, B. Wicinski, G. I. Lin, C. Bouras, P. Giannakopoulos, N. K. Robakis, John Morrison, D. P. Perl, P. R. Hof

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Although the presence of amyloid deposits is required to establish the neuropathologic diagnosis of Alzheimer's disease, from a clinical point of view, a direct contribution of these cerebral lesions to cognitive deficits is still controversial. The development and standardization of quantitative and accurate biochemical and neuropathologic methods may be critical to improve the postmortem diagnosis and clinicopathologic correlations. Here, we used a point counting method, based on the Cavalieri principle, to estimate the volume occupied by amyloid deposits in a discrete region of the prefrontal cortex and in the hippocampal formation, in brains from patients with cognitive status ranging from normal to severely demented. We demonstrate that the assessment of the total volume occupied by the amyloid deposits in the entorhinal cortex and subiculum can be considered an effective predictor of dementia severity. We also reveal the existence of a high degree of regional and interindividual heterogeneity in amyloid distribution and relative volume. Our data suggest that even though a correlation was observed between the stereologic point counting method and a non-stereologic random field thresholding approach, in most cases non-stereologic methods may not provide adequate samples of the tissue and may lead to unreliable estimates of amyloid burden due to the inhomogeneous distribution of amyloid in the cerebral cortex and the large variability among brains.

Original languageEnglish (US)
Pages (from-to)75-91
Number of pages17
JournalNeuroscience
Volume112
Issue number1
DOIs
StatePublished - Jun 12 2002
Externally publishedYes

Fingerprint

Amyloid Plaques
Alzheimer Disease
Amyloid
Hippocampus
Entorhinal Cortex
Brain
Prefrontal Cortex
Cerebral Cortex
Dementia

Keywords

  • Amyloid load
  • Cavalieri principle
  • Hippocampus
  • Immunohistochemistry
  • Neocortex
  • Quantitative neuropathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer’s disease. / Bussière, T.; Friend, P. D.; Sadeghi, N.; Wicinski, B.; Lin, G. I.; Bouras, C.; Giannakopoulos, P.; Robakis, N. K.; Morrison, John; Perl, D. P.; Hof, P. R.

In: Neuroscience, Vol. 112, No. 1, 12.06.2002, p. 75-91.

Research output: Contribution to journalArticle

Bussière, T, Friend, PD, Sadeghi, N, Wicinski, B, Lin, GI, Bouras, C, Giannakopoulos, P, Robakis, NK, Morrison, J, Perl, DP & Hof, PR 2002, 'Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer’s disease', Neuroscience, vol. 112, no. 1, pp. 75-91. https://doi.org/10.1016/S0306-4522(02)00056-8
Bussière, T. ; Friend, P. D. ; Sadeghi, N. ; Wicinski, B. ; Lin, G. I. ; Bouras, C. ; Giannakopoulos, P. ; Robakis, N. K. ; Morrison, John ; Perl, D. P. ; Hof, P. R. / Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer’s disease. In: Neuroscience. 2002 ; Vol. 112, No. 1. pp. 75-91.
@article{62fdce49035241b792a7b4ac9c749688,
title = "Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer’s disease",
abstract = "Although the presence of amyloid deposits is required to establish the neuropathologic diagnosis of Alzheimer's disease, from a clinical point of view, a direct contribution of these cerebral lesions to cognitive deficits is still controversial. The development and standardization of quantitative and accurate biochemical and neuropathologic methods may be critical to improve the postmortem diagnosis and clinicopathologic correlations. Here, we used a point counting method, based on the Cavalieri principle, to estimate the volume occupied by amyloid deposits in a discrete region of the prefrontal cortex and in the hippocampal formation, in brains from patients with cognitive status ranging from normal to severely demented. We demonstrate that the assessment of the total volume occupied by the amyloid deposits in the entorhinal cortex and subiculum can be considered an effective predictor of dementia severity. We also reveal the existence of a high degree of regional and interindividual heterogeneity in amyloid distribution and relative volume. Our data suggest that even though a correlation was observed between the stereologic point counting method and a non-stereologic random field thresholding approach, in most cases non-stereologic methods may not provide adequate samples of the tissue and may lead to unreliable estimates of amyloid burden due to the inhomogeneous distribution of amyloid in the cerebral cortex and the large variability among brains.",
keywords = "Amyloid load, Cavalieri principle, Hippocampus, Immunohistochemistry, Neocortex, Quantitative neuropathology",
author = "T. Bussi{\`e}re and Friend, {P. D.} and N. Sadeghi and B. Wicinski and Lin, {G. I.} and C. Bouras and P. Giannakopoulos and Robakis, {N. K.} and John Morrison and Perl, {D. P.} and Hof, {P. R.}",
year = "2002",
month = "6",
day = "12",
doi = "10.1016/S0306-4522(02)00056-8",
language = "English (US)",
volume = "112",
pages = "75--91",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer’s disease

AU - Bussière, T.

AU - Friend, P. D.

AU - Sadeghi, N.

AU - Wicinski, B.

AU - Lin, G. I.

AU - Bouras, C.

AU - Giannakopoulos, P.

AU - Robakis, N. K.

AU - Morrison, John

AU - Perl, D. P.

AU - Hof, P. R.

PY - 2002/6/12

Y1 - 2002/6/12

N2 - Although the presence of amyloid deposits is required to establish the neuropathologic diagnosis of Alzheimer's disease, from a clinical point of view, a direct contribution of these cerebral lesions to cognitive deficits is still controversial. The development and standardization of quantitative and accurate biochemical and neuropathologic methods may be critical to improve the postmortem diagnosis and clinicopathologic correlations. Here, we used a point counting method, based on the Cavalieri principle, to estimate the volume occupied by amyloid deposits in a discrete region of the prefrontal cortex and in the hippocampal formation, in brains from patients with cognitive status ranging from normal to severely demented. We demonstrate that the assessment of the total volume occupied by the amyloid deposits in the entorhinal cortex and subiculum can be considered an effective predictor of dementia severity. We also reveal the existence of a high degree of regional and interindividual heterogeneity in amyloid distribution and relative volume. Our data suggest that even though a correlation was observed between the stereologic point counting method and a non-stereologic random field thresholding approach, in most cases non-stereologic methods may not provide adequate samples of the tissue and may lead to unreliable estimates of amyloid burden due to the inhomogeneous distribution of amyloid in the cerebral cortex and the large variability among brains.

AB - Although the presence of amyloid deposits is required to establish the neuropathologic diagnosis of Alzheimer's disease, from a clinical point of view, a direct contribution of these cerebral lesions to cognitive deficits is still controversial. The development and standardization of quantitative and accurate biochemical and neuropathologic methods may be critical to improve the postmortem diagnosis and clinicopathologic correlations. Here, we used a point counting method, based on the Cavalieri principle, to estimate the volume occupied by amyloid deposits in a discrete region of the prefrontal cortex and in the hippocampal formation, in brains from patients with cognitive status ranging from normal to severely demented. We demonstrate that the assessment of the total volume occupied by the amyloid deposits in the entorhinal cortex and subiculum can be considered an effective predictor of dementia severity. We also reveal the existence of a high degree of regional and interindividual heterogeneity in amyloid distribution and relative volume. Our data suggest that even though a correlation was observed between the stereologic point counting method and a non-stereologic random field thresholding approach, in most cases non-stereologic methods may not provide adequate samples of the tissue and may lead to unreliable estimates of amyloid burden due to the inhomogeneous distribution of amyloid in the cerebral cortex and the large variability among brains.

KW - Amyloid load

KW - Cavalieri principle

KW - Hippocampus

KW - Immunohistochemistry

KW - Neocortex

KW - Quantitative neuropathology

UR - http://www.scopus.com/inward/record.url?scp=0037067074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037067074&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(02)00056-8

DO - 10.1016/S0306-4522(02)00056-8

M3 - Article

C2 - 12044473

AN - SCOPUS:0037067074

VL - 112

SP - 75

EP - 91

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 1

ER -