Acta Neuropathologica

, Volume 100, Issue 1, pp 29–35

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

  • Francisco García-Sierra
  • Jean J. Hauw
  • Charles Duyckaerts
  • Claude M. Wischik
  • José Luna-Muñoz
  • Raúl Mena
Regular paper

DOI: 10.1007/s004010051189

Cite this article as:
García-Sierra, F., Hauw, J., Duyckaerts, C. et al. Acta Neuropathol (2000) 100: 29. doi:10.1007/s004010051189

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.

Key words Alzheimer’s diseaseAT8Hyperphosphorylated tau proteinNeurofibrillarytanglesEntorhinal cortex

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Francisco García-Sierra
    • 1
  • Jean J. Hauw
    • 2
  • Charles Duyckaerts
    • 2
  • Claude M. Wischik
    • 3
  • José Luna-Muñoz
    • 1
  • Raúl Mena
    • 1
  1. 1.Department of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, PO Box 14-740, 07000, México, D. F., México e-mail: rmena@fisio.cinvestav.mx, Tel.: +525-747-7000 ext 5129; Fax: +525-747-7105
  2. 2.Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Salpêtrière, Paris, FranceFR
  3. 3.Department of Mental Health, University of Aberdeen, Aberdeen, UKGB