Many believe that engaging in novel and mentally challenging activities promotes brain health and prevents Alzheimer’s disease in later life. However, mental stimulation may also have risks as well as benefits. As neurons release neurotransmitters, they often also release amyloid peptides and tau proteins into the extracellular space. These by-products of neural activity can aggregate into the tau tangle and amyloid plaque signatures of Alzheimer’s disease. Over time, more active brain regions accumulate more pathology. Thus, increasing brain activity can have a cost. But the neuromodulator noradrenaline, released during novel and mentally stimulating events, may have some protective effects—as well as some negative effects. Via its inhibitory and excitatory effects on neurons and microglia, noradrenaline sometimes prevents and sometimes accelerates the production and accumulation of amyloid-β and tau in various brain regions. Both α2A- and β-adrenergic receptors influence amyloid-β production and tau hyperphosphorylation. Adrenergic activity also influences clearance of amyloid-β and tau. Furthermore, some findings suggest that Alzheimer’s disease increases noradrenergic activity, at least in its early phases. Because older brains clear the by-products of synaptic activity less effectively, increased synaptic activity in the older brain risks accelerating the accumulation of Alzheimer’s pathology more than it does in the younger brain.

许多人认为，参与新颖且具有智力挑战性的活动可以促进大脑健康，并在以后的生活中预防阿尔茨海默病。然而，精神刺激也可能有风险和好处。当神经元释放神经递质时，它们通常也会将淀粉样肽和 tau 蛋白释放到细胞外空间。这些神经活动的副产品可以聚集成阿尔茨海默病的 tau 蛋白缠结和淀粉样斑块特征。随着时间的推移，更活跃的大脑区域会积累更多的病理。因此，增加大脑活动是有代价的。但在新奇的精神刺激事件中释放的神经调节剂去甲肾上腺素可能会产生一些保护作用，同时也会产生一些负面影响。通过对神经元和小胶质细胞的抑制和兴奋作用，去甲肾上腺素有时会阻止、有时会加速不同大脑区域中β-淀粉样蛋白和 tau 蛋白的产生和积累。α2A 和 β 肾上腺素能受体都会影响淀粉样蛋白 β 的产生和 tau 蛋白过度磷酸化。肾上腺素能活性也会影响β-淀粉样蛋白和 tau 蛋白的清除。此外，一些研究结果表明，阿尔茨海默病会增加去甲肾上腺素能活性，至少在早期阶段是这样。由于老年大脑清除突触活动副产品的效率较低，因此老年大脑中突触活动的增加比年轻大脑中的突触活动更有可能加速阿尔茨海默病的积累。