However, in the prefrontal or temporal cortex of AD patients, the expression of aromatase
mRNA was found elevated in the astrocyte [50] and no changes in the neurons [161],
suggesting a cell type and regional specificity of brain estrogen synthesis. A reduction of
brain aromatase immunoreactivity is also identified in the hippocampus of AD patients
[159], but not in patients affected by epilepsy [57]. In contrast, during normal ageing, a clear
increase in aromatase immunoreactivity has been reported in the basal forebrain [158],
suggesting an age-related elevation of brain specific estrogen synthesis as a compensation of
circulating estrogen reduction in normal postmenopausal women. In concert to the theory
that maintaining healthy brain estrogen level is critical for preventing AD in females, studies
reported that APP transgenic mice with low brain estrogen developed earlier, and with more
severe AD pathology than ovariectomized APP mice [5]. Furthermore, a greater and better
neuroprotective response from estrogen treatment was found in APP mice with brain
estrogen deficiency compared to in the ovariectomized APP mice [66]. Together, evidences
suggest an important role of brain estrogen in female risk of developing AD.