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This phase 2b/3 trial evaluated the effects of plasma exchange (PE) with albumin replacement on patients with mild-to-moderate Alzheimer’s disease (AD). A total of 347 patients were randomized into three This study challenges the idea that young blood is necessary for tissue rejuvenation, showing instead that “neutral blood exchange” (NBE) — replacing half of an animal’s plasma with saline and 5% albumin — can rejuvenate aged tissues. In old mice, a single NBE session matched or exceeded the rejuvenative effects seen in heterochronic blood sharing, enhancing muscle repair, reducing liver fat and fibrosis, and increasing hippocampal neurogenesis.

Proteomic analysis of NBE-treated mice and a similar human procedure, therapeutic plasma exchange (TPE), showed a “molecular reset” of systemic signaling, increasing proteins associated with tissue repair and immune responses. Interestingly, albumin itself did not appear to be the main rejuvenative factor, as its levels did not change significantly with age or with NBE/TPE treatments. Instead, the study suggests that diluting age-elevated autoregulatory proteins impacts multiple signaling pathways, leading to lasting molecular and functional benefits.

The findings indicate that TPE, an FDA-approved procedure, could be used to promote health and resilience in older adults by resetting the systemic signaling environment, providing an immediate application for improving aging-related outcomes.