Transfusing blood from old mice accelerates Alzheimer's progression in an animal model

Alzheimer's disease is the most common form of dementia worldwide and continues to be one of the greatest public health challenges. New research, published in the journal Aging-US, reveals that blood from aged mice can accelerate the progression of the disease, while young blood may have protective effects. The study was led by researchers from Instituto Latinoamericano de Salud Cerebral (BrainLat) at Universidad Adolfo Ibáñez in conjunction with MELISA Institute, the University of Texas Health Science Center at Houston, and Universidad Mayor.

Alzheimer's is characterized by the abnormal accumulation of beta-amyloid protein (Aβ) in the brain, forming plaques that disrupt communication between neurons and generate neurodegenerative processes. Although this protein originates in the central nervous system, recent studies have suggested that it may also be present in the blood, opening new possibilities for understanding how the disease progresses.

To explore this hypothesis, the team used Tg2576 transgenic mice (a model widely used in Alzheimer's research), which received weekly blood infusions from young and old mice for 30 weeks to assess whether factors present in the blood could modulate amyloid accumulation and the animals' behavior.

“This collaborative work between various institutions reinforces the importance of understanding how systemic factors condition the brain environment and directly impact mechanisms that promote disease progression. By demonstrating that peripheral signals derived from aged blood can modulate central processes in the pathophysiology of Alzheimer's, these findings open new opportunities to study therapeutic targets aimed at the blood-brain axis,” explained Dr. Claudia Durán-Aniotz, from the Instituto Latinoamericano de Salud Cerebral (BrainLat) at Universidad Adolfo Ibáñez.

The team assessed cognitive performance using the Barnes test, the accumulation of amyloid plaques with histological and biochemical techniques, and performed a comprehensive proteomic analysis of the treated brains. This analysis revealed more than 250 differentially expressed proteins, linked to synaptic functions, endocannabinoid signaling, and calcium channels, which could explain the observed changes.

Regarding MELISA Institute's participation in this research, Mauricio Hernández, a proteomics expert at the research and biotechnology center, commented that “within this study, we conducted a large-scale proteomic analysis that allowed us to generate excellent quality data in this complex matrix like plasma, a technical challenge for any proteomics laboratory. Thanks to our state-of-the-art equipment (timsTOF Pro2), we are proud to have contributed to the production of a robust and high-quality scientific article.”

These results reinforce the idea that circulating factors in the blood can directly influence the progression of neurodegenerative diseases such as Alzheimer's. Understanding these mechanisms will allow for the identification of new therapeutic targets and preventative strategies. The next step will be to determine exactly what these factors are and whether it is possible to intervene in them in humans.

“It is a pleasure to contribute our proteomic capabilities to support innovative research initiatives like this study, which allow us to advance the knowledge and development of new therapies for neurodegenerative diseases, which are currently a global health problem,” emphasized Dr. Elard Koch, Chairman of MELISA Institute.

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C.DA. was supported by ANID/FONDECYT Regular 1210622, ANID/PIA/ANILLOS ACT210096, the Alzheimer’s Association (AARGD-24-1310017), ANID/FOVI240065 and ANID/Proyecto Exploracion 13240170 and MULTI-PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA (ReDLat), supported by NIH research grant R01AG057234 funded by the National Institute of Aging (NIA) and the Fogarty International Center (FIC), an Alzheimer’s Association grant (SG-20-725707-ReDLat), the Rainwater Charitable Foundation, and the Global Brain Health Institute with additional support from the Bluefield Project to Cure Frontotemporal Dementia, an NIH contract (75NS95022C00031), and NIA under awards R01AG075775, R01AG082056, and R01AG083799. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health, the Alzheimer’s Association, Rainwater Charitable Foundation, Bluefield Project to Cure Frontotemporal Dementia, or the Global Brain Health Institute. The contribution of RM and team in this work was supported by NIH grants RF1AG072491 and RF1AG059321. UW was supported by ANID/FONDECYT Regular 1240176.

Matias Pizarro (1, 2), Ruben Gomez-Gutierrez (3), Ariel Caviedes (1), Catalina Valdes (3), Ute Woehlbier (4), Cristian Vargas (5), Mauricio Hernandez (5), Claudia Duran-Aniotz (1), Rodrigo Morales (3, 6).

(1) Latin American Institute for Brain Health (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile; (2) Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibanez, Santiago, Chile; (3) Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (4) Center for Integrative Biology (CIB), Universidad Mayor, Santiago, Chile; (5) Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Bio-Bio, Chile; (6) Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O’Higgins, Santiago, Chile.