摘要β- Amyloid (Aβ) is a specific pathological hallmark of Alzheimer's disease (AD). Because of its neurotoxicity, AD patients exhibit multiple brain dysfunctions. Disease- modifying therapy (DMT) is the central concept in the development of AD thera-peutics today, and most DMT drugs that are currently in clinical trials are anti- Aβ drugs, such as aducanumab and lecanemab. Therefore, understanding Aβ's neurotoxic mechanism is crucial for Aβ- targeted drug development. Despite its total length of only a few dozen amino acids, Aβ is incredibly diverse. In addition to the well- known Aβ 1- 42 , N- terminally truncated, glutaminyl cyclase (QC) catalyzed, and pyroglutamate- modified Aβ (pEAβ) is also highly amyloidogenic and far more cytotoxic. The extracel-lular monomeric Aβ x- 42 (x = 1– 11) initiates the aggregation to form fibrils and plaques and causes many abnormal cellular responses through cell membrane receptors and receptor- coupled signal pathways. These signal cascades further influence many cel-lular metabolism- related processes, such as gene expression, cell cycle, and cell fate, and ultimately cause severe neural cell damage. However, endogenous cellular anti- Aβ defense processes always accompany the Aβ-i nduced microenvironment alterations. Aβ- cleaving endopeptidases, Aβ- degrading ubiquitin- proteasome system (UPS), and Aβ- engulfing glial cell immune responses are all essential self- defense mechanisms that we can leverage to develop new drugs. This review discusses some of the most recent advances in understanding Aβ- centric AD mechanisms and suggests prospects for promising anti- Aβ strategies.