Acta Neuropathologica

, Volume 119, Issue 5, pp 543–554

Analysis of microdissected human neurons by a sensitive ELISA reveals a correlation between elevated intracellular concentrations of Aβ42 and Alzheimer’s disease neuropathology

  • Masakazu Hashimoto
  • Nenad Bogdanovic
  • Inga Volkmann
  • Mikio Aoki
  • Bengt Winblad
  • Lars O. Tjernberg
Original Paper

DOI: 10.1007/s00401-010-0661-6

Cite this article as:
Hashimoto, M., Bogdanovic, N., Volkmann, I. et al. Acta Neuropathol (2010) 119: 543. doi:10.1007/s00401-010-0661-6

Abstract

In Alzheimer’s disease (AD), Purkinje neurons in the cerebellum are spared, while, for instance, pyramidal neurons in the hippocampus are neuropathologically affected. Several lines of evidence suggest that the pathogenesis could be induced by the concentration-dependent polymerization of the amyloid β-peptide (Aβ) into extracellular oligomers. The role of intracellular Aβ is not fully investigated, but recent data indicate that also this pool could be of importance. Here, we use laser capture microdissection microscopy for isolation of Purkinje neurons from AD cases and controls, and quantify the low levels of intracellular Aβ using a novel and highly sensitive ELISA. Similar to Cornu Ammonis 1 pyramidal neurons, the intracellular levels of the most toxic variant, Aβ42, as well as the Aβ42/Aβ40 ratio, were increased in Purkinje neurons from sporadic AD cases as compared to controls. However, the levels of Aβ42 as well as Aβ40 were clearly lower in Purkinje neurons than in pyramidal neurons. Based on the volume of the captured Purkinje neurons, the intraneuronal concentrations of Aβ42 were calculated to be 200 nM in sporadic AD cases and 90 nM in controls. The corresponding concentrations in pyramidal neurons from hippocampus were 3 μM and 660 nM, respectively. The Aβ40 concentration was not significantly altered in AD cases compared to controls. However, we found ten times higher concentration of Aβ40 in pyramidal neurons (10 μM) compared to Purkinje neurons (1 μM). Finally, we suggest that high concentration of intracellular Aβ42 correlates with vulnerability to AD neuropathology.

Keywords

Alzheimer’s disease Aβ40 Aβ42 Laser capture microdissection ELISA Purkinje neuron 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Masakazu Hashimoto
    • 1
  • Nenad Bogdanovic
    • 2
  • Inga Volkmann
    • 1
  • Mikio Aoki
    • 1
    • 3
  • Bengt Winblad
    • 1
  • Lars O. Tjernberg
    • 1
  1. 1.Department of Neurobiology, Care Sciences and Society (NVS)Karolinska Institutet and Dainippon Sumitomo Pharma Alzheimer Center (KASPAC), KI-Alzheimer’s Disease Research Center, Karolinska InstitutetHuddingeSweden
  2. 2.Section of Clinical Geriatrics, Department of Neurobiology, Care Science and Society (NVS)Karolinska Institutet, Karolinska University Hospital HuddingeHuddingeSweden
  3. 3.Genomic Science LaboratoriesDainippon Sumitomo Pharma Co. LtdOsakaJapan

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