image: Figure 1. Schematic representation of the blood infusion regime (blood from old and young wild type mice into Tg2576 mice). Wild-type mice aged 50–75 days (WT Young mice), and wild-type mice aged 443–532 days (WT Old mice) served as blood donors. This blood was transfused to 120-day-old Tg2576 mice, which then underwent to weekly transfusions and sacrificed at 363–366 days old. Before sacrificing, mice were evaluated for spatial memory. Postmortem analyses included immunopathological, biochemical, and proteomic evaluations of brain tissues.
Credit: Copyright: © 2025 Pizarro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“This study highlights the influence of blood in AD pathology and the identification of potential therapeutic targets.”
BUFFALO, NY — December 8, 2025 — A new research paper was published in Volume 17, Issue 11 of Aging-US on September 12, 2025, titled “Infusion of blood from young and old mice modulates amyloid pathology.”
This study was led by co-first authors Matias Pizarro from Universidad Adolfo Ibáñez and Ruben Gomez-Gutierrez from The University of Texas Health Science Center at Houston, alongside corresponding authors Claudia Duran-Aniotz from Universidad Adolfo Ibáñez and Rodrigo Morales from The University of Texas Health Science Center at Houston and Universidad Bernardo O’Higgins. The goal was to investigate how blood from young and old mice influences Alzheimer’s-related changes in a transgenic mouse model. The findings indicate that age-dependent circulating factors can either worsen or mitigate brain changes associated with dementia, highlighting blood and its components as potential therapeutic targets.
Alzheimer’s disease is a progressive neurodegenerative disorder characterized by misfolded amyloid proteins, inflammation, and gradual cognitive decline, with aging as its main risk factor. In this work, whole blood from young adult or very old wild-type mice was repeatedly infused into Tg2576 mice, a well-established model of amyloid accumulation and memory impairment. Over several months, recipient mice received 30 weekly blood infusions, followed by behavioral testing and detailed neuropathological analyses.
“Tg2576 mice express the human APP harboring the Swedish mutation.”
Mice that received blood from old donors performed worse in both short- and long-term spatial memory tasks than mice infused with young blood, suggesting that aged blood contains factors that impair cognition. When the team examined brain tissue, they found more cortical amyloid deposits detected by a specific antibody in mice treated with old blood, while overall amyloid levels measured biochemically did not change, suggesting differences in plaque type or compactness rather than total amount. The expression of amyloid precursor protein in the brain was also higher after old-blood infusion, which may partly explain the shift in amyloid pathology.
Despite these changes in plaques and memory, classical markers of astrocyte activation, a sign of brain inflammation, did not differ between groups, pointing to more subtle molecular shifts. A broad proteomic analysis of brain samples revealed dysregulation of proteins involved in synapse formation, calcium signaling, and the endocannabinoid system, pathways important for neuronal communication and plasticity. Among them, the calcium channel–related protein CACNA2D2 and the signaling protein BRAF were increased in mice that received old blood, confirming that aged blood circulation can reshape key signaling networks linked to neuronal function and degeneration.
Overall, this study supports the idea that blood is not just a passive carrier but a powerful modulator of brain health during aging and disease. While young blood has been associated in previous work with improved synaptic function and reduced amyloid and tau changes, this study emphasizes the harmful impact of old blood, particularly on cortical amyloid patterns and memory. The identification of CACNA2D2 and BRAF as potential mediators of these effects suggests new avenues for targeting blood-borne factors or downstream brain pathways to slow or modify Alzheimer’s-related decline.
Paper DOI: https://doi.org/10.18632/aging.206319
Corresponding authors: Claudia Duran-Aniotz – Claudia.Duran@uai.cl; Rodrigo Morales – Rodrigo.MoralesLoyola@uth.tmc.edu
Abstract video: https://www.youtube.com/watch?v=zsBDSAipH3w
Keywords: aging, Alzheimer’s disease, amyloid-β, neurodegeneration, protein misfolding, blood infusion, therapeutic targets
Click here to sign up for free Altmetric alerts about this article.
______
To learn more about the journal, please visit www.Aging-US.com and connect with us on social media:
- X
- YouTube
- Bluesky
- Spotify, and available wherever you listen to podcasts
Click here to subscribe to Aging-US publication updates.
For media inquiries, please contact media@impactjournals.com.
Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Infusion of blood from young and old mice modulates amyloid pathology
Article Publication Date
12-Sep-2025
COI Statement
The authors declare no conflicts of interest related to this study.