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The medial mamillary nucleus (MMN) is an important hub in memory circuits. In the present study, we aimed at determining MMN neuronal nuclear and pericaryal sizes that are informative about the neuronal metabolic activity in Alzheimer's disease (AD) in vascular dementia (VD) patients. Both parameters were significantly larger in VD than in control patients (p<0.01) and were not different from those in AD subjects. Neuronal nuclei (p<0.05), but not pericarya were larger in AD than in control patients. Neuronal nuclei and pericarya were larger if nuclear ERα staining was present. The intensity of ERα in the neuronal nuclei was significantly correlated with both nuclear and pericaryal sizes (p<0.007). The only exception was the strongest ERα staining providing a totally black cover over the nucleus that was increased in AD patients. In this case the nuclei and pericarya were smaller than in moderate intensity staining that allowed visualization of the nucleolus and large chromatin clumps. Our data show for the first time prominent activation of MMN neurons in VD and to a lesser degree in AD that may be mediated by nuclear ERα. Our findings are in agreement with the idea that neuronal activation may protect against AD neuropathological alterations.

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