The extent of neurofibrillary pathology in perforant pathway neurons is the key determinant of dementia in the very old

F Garcia-Sierra, J J Hauw, C Duyckaerts, C M Wischik, J Luna-Munoz, R Mena

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Abstract

Neurofibrillary pathology as found in Alzheimer's disease (AD) is also found in the normal elderly, suggesting that these changes may be part of the aging process. In this study, we assessed the densities and distribution of structures recognized by the monoclonal antibody (mAb) to phosphorylated tau (AT8) in the hippocampal formation and medial temporal isocortex of 19 centenarians. Of these, 4 cases were demented and 15 non-demented. AT8 immunoreactivity correlated with the global deterioration scale (GDS). The density of both intraneuronal neurofibrillary tangles (I-NFTs) and neuritic clusters (NCs) significantly correlated with the GDS in the layer II of the entorhinal cortex (r = 0.66, P = 0.005 and r = 0.611, P = 0.01, respectively). Density of I-NFTs in the subiculum (r = 0.491; P = 0.034) also correlated significantly. No other area was found to be statistically significant. Importantly, no correlation was found when demented and non-demented centenarian cases were analyzed separately, suggesting that the difference marks a fundamental shift between AD and non-demented individuals. This assertion is supported by the significantly higher densities of I-NFTs and NCs in the transentorhinal (P = 0.043 and P = 0.011, respectively) and layer II of the entorhinal cortex (P = 0.02 and P = 0.007, respectively), and I-NFTs in the subiculum (P < 0.001) and CA1 (P = 0.011) in the demented group when compared with the non-demented cases. Granular diffuse deposits, an early stage parameter of the neurofibrillary pathology involving accumulation of non-fibrillar abnormally phosphorylated tau protein did not correlate with the GDS or between the two groups studied. This study, combining morphometric and confocal analyses, not only provides further evidence that, in the brains of patients with AD, the perforant pathway is highly sensitive to tau pathology but also that involvement is distinct from the changes of normal aging, even of the oldest old.

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalActa Neuropathologica
Volume100
Publication statusPublished - 2000

Keywords

  • Alzheimer's disease
  • AT8
  • hyperphosphorylated tau protein
  • neurofibrillary tangles
  • entorhinal cortex
  • PAIRED HELICAL FILAMENTS
  • MILD ALZHEIMERS-DISEASE
  • 20 FRENCH CENTENARIANS
  • TAU-PROTEIN
  • CEREBRAL-CORTEX
  • SENILE PLAQUES
  • REGIONAL DISTRIBUTION
  • AUTOPSY POPULATION
  • TANGLES
  • BRAINS

Cite this

The extent of neurofibrillary pathology in perforant pathway neurons is the key determinant of dementia in the very old. / Garcia-Sierra, F ; Hauw, J J ; Duyckaerts, C ; Wischik, C M ; Luna-Munoz, J ; Mena, R .

In: Acta Neuropathologica, Vol. 100, 2000, p. 29-35.

Research output: Contribution to journalArticle

Garcia-Sierra, F ; Hauw, J J ; Duyckaerts, C ; Wischik, C M ; Luna-Munoz, J ; Mena, R . / The extent of neurofibrillary pathology in perforant pathway neurons is the key determinant of dementia in the very old. In: Acta Neuropathologica. 2000 ; Vol. 100. pp. 29-35.
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AU - Garcia-Sierra, F

AU - Hauw, J J

AU - Duyckaerts, C

AU - Wischik, C M

AU - Luna-Munoz, J

AU - Mena, R

PY - 2000

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N2 - Neurofibrillary pathology as found in Alzheimer's disease (AD) is also found in the normal elderly, suggesting that these changes may be part of the aging process. In this study, we assessed the densities and distribution of structures recognized by the monoclonal antibody (mAb) to phosphorylated tau (AT8) in the hippocampal formation and medial temporal isocortex of 19 centenarians. Of these, 4 cases were demented and 15 non-demented. AT8 immunoreactivity correlated with the global deterioration scale (GDS). The density of both intraneuronal neurofibrillary tangles (I-NFTs) and neuritic clusters (NCs) significantly correlated with the GDS in the layer II of the entorhinal cortex (r = 0.66, P = 0.005 and r = 0.611, P = 0.01, respectively). Density of I-NFTs in the subiculum (r = 0.491; P = 0.034) also correlated significantly. No other area was found to be statistically significant. Importantly, no correlation was found when demented and non-demented centenarian cases were analyzed separately, suggesting that the difference marks a fundamental shift between AD and non-demented individuals. This assertion is supported by the significantly higher densities of I-NFTs and NCs in the transentorhinal (P = 0.043 and P = 0.011, respectively) and layer II of the entorhinal cortex (P = 0.02 and P = 0.007, respectively), and I-NFTs in the subiculum (P < 0.001) and CA1 (P = 0.011) in the demented group when compared with the non-demented cases. Granular diffuse deposits, an early stage parameter of the neurofibrillary pathology involving accumulation of non-fibrillar abnormally phosphorylated tau protein did not correlate with the GDS or between the two groups studied. This study, combining morphometric and confocal analyses, not only provides further evidence that, in the brains of patients with AD, the perforant pathway is highly sensitive to tau pathology but also that involvement is distinct from the changes of normal aging, even of the oldest old.

AB - Neurofibrillary pathology as found in Alzheimer's disease (AD) is also found in the normal elderly, suggesting that these changes may be part of the aging process. In this study, we assessed the densities and distribution of structures recognized by the monoclonal antibody (mAb) to phosphorylated tau (AT8) in the hippocampal formation and medial temporal isocortex of 19 centenarians. Of these, 4 cases were demented and 15 non-demented. AT8 immunoreactivity correlated with the global deterioration scale (GDS). The density of both intraneuronal neurofibrillary tangles (I-NFTs) and neuritic clusters (NCs) significantly correlated with the GDS in the layer II of the entorhinal cortex (r = 0.66, P = 0.005 and r = 0.611, P = 0.01, respectively). Density of I-NFTs in the subiculum (r = 0.491; P = 0.034) also correlated significantly. No other area was found to be statistically significant. Importantly, no correlation was found when demented and non-demented centenarian cases were analyzed separately, suggesting that the difference marks a fundamental shift between AD and non-demented individuals. This assertion is supported by the significantly higher densities of I-NFTs and NCs in the transentorhinal (P = 0.043 and P = 0.011, respectively) and layer II of the entorhinal cortex (P = 0.02 and P = 0.007, respectively), and I-NFTs in the subiculum (P < 0.001) and CA1 (P = 0.011) in the demented group when compared with the non-demented cases. Granular diffuse deposits, an early stage parameter of the neurofibrillary pathology involving accumulation of non-fibrillar abnormally phosphorylated tau protein did not correlate with the GDS or between the two groups studied. This study, combining morphometric and confocal analyses, not only provides further evidence that, in the brains of patients with AD, the perforant pathway is highly sensitive to tau pathology but also that involvement is distinct from the changes of normal aging, even of the oldest old.

KW - Alzheimer's disease

KW - AT8

KW - hyperphosphorylated tau protein

KW - neurofibrillary tangles

KW - entorhinal cortex

KW - PAIRED HELICAL FILAMENTS

KW - MILD ALZHEIMERS-DISEASE

KW - 20 FRENCH CENTENARIANS

KW - TAU-PROTEIN

KW - CEREBRAL-CORTEX

KW - SENILE PLAQUES

KW - REGIONAL DISTRIBUTION

KW - AUTOPSY POPULATION

KW - TANGLES

KW - BRAINS

M3 - Article

VL - 100

SP - 29

EP - 35

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

ER -