Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
Alzheimers Dement. 2023 Sep;19(9):3848-3857. doi: 10.1002/alz.13037. Epub 2023 Mar 24.
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.
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.
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.
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.
Local estrogen system is activated with age only in women's entorhinal cortex (EC). EC neuronal activity increased with age only in elderly women with intact cognition. Men and women have different molecular strategies to retain cognition with aging. P-tau accumulation in the EC was higher and faster in cognitively intact elderly women.
女性比男性更容易患阿尔茨海默病（AD）。内嗅皮层（EC）是 AD 最早受影响的结构之一。我们在认知正常的老年人中发现，EC 中与年龄相关的分子变化不同。
通过定量免疫组织化学或原位杂交，确定 EC 中与年龄相关的 12 种特征分子的变化。它们被任意分为与性激素相关的分子、神经元活动标志物、神经递质相关分子和胆碱能活性相关分子。
分子的变化表明，与年龄相关的女性 EC 中局部雌激素和神经元活性增加，同时出现更快更高的磷酸化 tau 积累，而男性 EC 中局部雌激素/雄激素和神经元活性主要保持稳定。
EC 在女性和男性中采用不同的神经生物学策略来维持认知功能，这似乎伴随着女性 AD 的更早发作。
只有女性的内嗅皮层（EC）中的局部雌激素系统随年龄而激活。只有认知正常的老年女性，EC 中的神经元活动才会随年龄增长而增加。男性和女性在衰老过程中保持认知能力的分子策略不同。认知正常的老年女性 EC 中的 p-tau 积累更高且更快。
