Dementia, a prevalent condition among older individuals, has profound societal implications. Extensive research has resulted in no cure for what is perceived as the most common dementing illness: Alzheimer disease (AD). AD is defined by specific brain abnormalities — amyloid-β plaques and tau protein neurofibrillary tangles — that are proposed to actively influence the neurodegenerative process. However, conclusive evidence of amyloid-β toxicity is lacking, the mechanisms leading to the accumulation of plaques and tangles are unknown, and removing amyloid-β has not halted neurodegeneration. So, the question remains, are we making progress towards a solution? The complexity of AD is underscored by numerous genetic and environmental risk factors, and diverse clinical presentations, suggesting that AD is more akin to a syndrome than to a traditional disease, with its pathological manifestation representing a convergence of pathogenic pathways. Therefore, a solution requires a multifaceted approach over a single ‘silver bullet’. Improved recognition and classification of conditions that converge in plaques and tangle accumulation and their treatment requires the use of multiple strategies simultaneously.

痴呆症是老年人中普遍存在的疾病，具有深远的社会影响。广泛的研究表明，最常见的痴呆症——阿尔茨海默病（AD）仍无法治愈。AD 是由特定的大脑异常（淀粉样蛋白斑块和 tau 蛋白神经原纤维缠结）定义的，这些异常被认为会积极影响神经退行性过程。然而，β-淀粉样蛋白毒性的确凿证据尚缺乏，导致斑块和缠结积聚的机制尚不清楚，去除β-淀粉样蛋白并不能阻止神经退行性变。所以，问题仍然是，我们在解决问题方面是否取得了进展？众多的遗传和环境危险因素以及多样化的临床表现凸显了 AD 的复杂性，这表明 AD 更类似于一种综合征，而不是一种传统疾病，其病理表现代表了多种致病途径的融合。因此，解决方案需要采用多方面的方法，而不是单一的“银弹”。提高对斑块和缠结聚集病症的识别和分类及其治疗需要同时使用多种策略。