Preventive and therapeutic reduction of amyloid deposition and behavioral impairments in a model of Alzheimer’s disease by whole blood exchange
Open accessAbstract
Alzheimer's disease (AD) is the major form of dementia in the elderly population. The main neuropathological changes in AD patients are neuronal death, synaptic alterations, brain inflammation, and the presence of cerebral protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Compelling evidence suggests that the misfolding, aggregation, and cerebral deposition of amyloid-beta (Aβ) plays a central role in the disease. Thus, prevention and removal of misfolded protein aggregates is considered a promising strategy to treat AD. In the present study, we describe that the development of cerebral amyloid plaques in a transgenic mice model of AD (Tg2576) was significantly reduced by 40-80% through exchanging whole blood with normal blood from wild type mice having the same genetic background. Importantly, such reduction resulted in improvement in spatial memory performance in aged Tg2576 mice. The exact mechanism by which blood exchange reduces amyloid pathology and improves memory is presently unknown, but measurements of Aβ in plasma soon after blood exchange suggest that mobilization of Aβ from the brain to blood may be implicated. Our results suggest that a target for AD therapy may exist in the peripheral circulation, which could open a novel disease-modifying intervention for AD.
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Whole blood replacement lowers soluble Aβ levels in the blood and Aβ deposits in the brains of aged mice and markedly improves spatial memory.
“Whole blood replacement mainly lowers soluble Aβ levels in the blood and Aβ deposits in the brains of aged mice and markedly improves spatial memory.453”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [453]
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Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
- Authors
- Urayama, A., Moreno-Gonzalez, I., Morales-Scheihing, D., Kharat, V., Pritzkow, S., & Soto, C.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Urayama, Akihiko
- Soto, Claudio
- Venue
- Molecular Psychiatry
- Published
- 2022-07-15
- Volume
- 27
- Issue
- 10
- Pages
- 4285-4296
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC10601825
- OpenAlex
- W4285491715
- Cited by
- 37
- References
- 39
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 8 · 2023: 9 · 2022: 1
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, other-oa)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (R01AG059321)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, amyloid plaques, Tg2576 mice, transgenic mouse model, spatial memory, behavioral impairment, disease-modifying therapy, peripheral circulation
- MeSH terms
- Aged, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Mice, Transgenic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Plaque, Amyloid, Protein Aggregates
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