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Sexually dimorphic age-related molecular differences in the entorhinal cortex of cognitively intact elderly: Relation to early Alzheimer's changes

Xin-Lu Chen, Jennifer Monteiro Fortes, Yu-Ting Hu, Juliet van Iersel, Kang-Ning He, Joop van Heerikhuize, Rawien Balesar, Dick Swaab, Ai-Min Bao

Alzheimer's & dementia : the journal of the Alzheimer's Association(2023)

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Abstract
Introduction: Women are more vulnerable to Alzheimer's disease (AD) than men. The entorhinal cortex (EC) is one of the earliest structures affected in AD. We identified in cognitively intact elderly different molecular changes in the EC in relation to age. Methods: Changes in 12 characteristic molecules in relation to age were determined by quantitative immunohistochemistry or in situ hybridization in the EC. They were arbitrarily grouped into sex steroid-related molecules, markers of neuronal activity, neurotransmitter-related molecules, and cholinergic activity-related molecules. Results: The changes in molecules indicated increasing local estrogenic and neuronal activity accompanied by a higher and faster hyperphosphorylated tau accumulation in women's EC in relation to age, versus a mainly stable local estrogenic/androgenic and neuronal activity in men's EC. Discussion: EC employs a different neurobiological strategy in women and men to maintain cognitive function, which seems to be accompanied by an earlier start of AD in women.
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Key words
Alzheimer's disease,entorhinal cortex,neuronal activity,sex difference,sex steroids
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