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Decreased estrogen receptor-α expression in hippocampal neurons in relation to hyperphosphorylated tau in Alzheimer patients

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Abstract

Emerging evidence has demonstrated the neuroprotection of estrogen in Alzheimer's disease (AD). The hippocampus, an important target of estrogen action, is severely affected in the Alzheimer process. The aim of present study was to detect the distribution of estrogen receptor-α (ER-α) and the relationship between ER-α-containing neurons and the pretangles stained by Alz-50 in the hippocampus of AD patients. The results showed that more than half of hippocampal neurons expressed ER-α. The number of cytoplasmic ER-α-positive neurons was significantly decreased in the CA1 and CA2 subfields of AD hippocampus, but the ratio of these ER-α-expressing neurons to the nucleolated neuronal profiles stained by thionin was not different between the two groups. Interestingly, the number of nuclear ER-α-staining neurons was also markedly decreased in the CA1 and CA2 subfields of AD hippocampus, and the percentage of these nuclear staining neurons was also significantly decreased in the same subfields. Furthermore, some double-labeled neurons containing ER-α and Alz-50 were found in AD patients. However, in these double-labeled neurons, ER-α was only located in the cytoplasm. Thus, we hypothesize that the nuclear ER-α may play more important roles of neuroprotection during the process of AD.

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Acknowledgements

We are grateful to the Netherlands Brain Bank for the brain material, and to Ms. Hong-Yue Ju and Huai-Yu Zhang for experimental help. This project was financially supported by the National Natural Science Foundation of China (30070826), the National Key Project for Basic Science of China (G1999054007), the KNAW 02CDP014, the Innovation Project of Science Academy of China (KSCX2-SW-217), and the International Cooperation Project of China (2001CB711101).

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Correspondence to Jiang-Ning Zhou.

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Hu, XY., Qin, S., Lu, YP. et al. Decreased estrogen receptor-α expression in hippocampal neurons in relation to hyperphosphorylated tau in Alzheimer patients. Acta Neuropathol 106, 213–220 (2003). https://doi.org/10.1007/s00401-003-0720-3

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  • DOI: https://doi.org/10.1007/s00401-003-0720-3

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