Alzheimer’s disease (AD) is the most common cause of dementia and remains a major global health challenge. In 2023, lecanemab—the first therapeutic drug targeting amyloid pathology in AD—was approved in Japan. However, its clinical efficacy is limited, highlighting the urgent need for more effective treatments and reliable diagnostic biomarkers to identify suitable treatment candidates. The mechanisms underlying the formation and progression of AD pathology are still not fully understood. Amyloid pathology involves the aggregation of amyloid β protein (Aβ) in the brain, leading to the formation of amyloid plaques. This aggregation may be induced by the binding of gangliosides present on the membrane of cell membranes and extracellular vesicles (EVs) to Aβ [1] (Fig. 58.1). Imaging mass spectrometry (MS) has demonstrated the co-localization of gangliosides (GM1, GM2, GM3) within amyloid plaques [2]. Moreover, the membrane of EVs (particularly exosomes) are known to be enriched in gangliosides compared to those of parent cell, suggesting a potential role for EV-associated gangliosides in amyloid formation [3, 4]. A subset of EVs produced in the brain can cross into the bloodstream, making them promising candidates for blood-based biomarkers of brain diseases. In AD model mouse, it has been reported that blood levels of EVs containing GM1 gangliosides—capable of binding Aβ—fluctuate in response to amyloid accumulation in the brain [5].