Hippocampal estrogen receptor-alpha splice variant TADDI in the human brain in aging and Alzheimer's disease.

ABSTRACT

BACKGROUND/AIMS: Estrogen receptor-alpha (ER alpha) splice variants are important for understanding estrogen effects on the brain and estrogen therapy pitfalls. We addressed the question whether a novel ER alpha splice variant TADDI is expressed at the protein level in the human brain and whether it changes in relation to aging and Alzheimer's disease (AD). METHODS: Immunoreactivity (-ir) for TADDI was assessed on postmortem human brain material from a total of 116 cases. RESULTS: The highest levels of this splice form were found in the hypothalamic supraoptic nucleus (SON), pontine nuclei, medulla oblongata, gray matter of the spinal cord, the hippocampus, glomeruli of the cerebellum, the nucleus basalis of Meynert (NBM), and the tuberomamillary nucleus (TMN). TADDI-ir was mainly confined to the cytoplasm but was also determined in the nuclei of hippocampal neurons from young patients. In the hippocampus, the NBM, and the TMN, TADDI-ir was higher in postmenopausal women than in women brain areas and in the SON, it was diminished in AD women. In the NBM of AD men, TADDI-ir was enhanced.

CONCLUSION:

Aging- and AD-related changes in TADDI-ir show that it should be considered for the sensitivity of the neural tissue to estrogen therapy.