Immunomodulation targeting of both Aβ and tau pathological conformers ameliorates Alzheimer’s disease pathology in TgSwDI and 3xTg mouse models
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BACKGROUND: Central to the pathogenesis of Alzheimer's disease (AD) and many other neurodegenerative diseases is the conformational change of a normal self-protein into toxic oligomeric species and amyloid deposits. None of these disorders have an effective therapy, but immunization approaches hold great promise. We have previously shown that active immunization with a novel peptide when polymerized into a stable oligomeric conformation, pBri, induced a humoral immune response to toxic Aβ species in an AD model, APP/PS1 transgenic (Tg) mice, reducing plaque deposits. pBri is a glutaraldehyde polymerized form of the carboxyl fragment of an amyloidogenic protein, which is deposited in the brains of patients with a rare autosomal dominant disease due to a missense mutation in a stop codon, resulting in the translation of an intronic sequence, with no known sequence homology to any mammalian protein. METHODS: In the current study we tested whether pBri-peptide-based immunomodulation is effective at reducing both vascular amyloid deposits and tau-related pathology using TgSwDI mice with extensive congophilic angiopathy and 3xTg mice with tau pathology. RESULTS: Our results indicate that this immunomodulation approach, which produces a humoral response to proteins in a pathological conformation, is effective at reducing both Aβ and tau-related pathologies. CONCLUSIONS: This immunomodulatory approach has the advantage of using a non-self-immunogen that is less likely to be associated with autoimmune toxicity. Furthermore we found that it is able to target all the cardinal features of AD concurrently.
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Active immunization uses Aβ, phosphorylated tau (ptau) peptides, or specific artificial peptides such as polymerized British amyloidosis (ABri)-related peptide (pBri) as immunogens.
“Aβ, phosphorylated tau (ptau) peptides, or specific artificial peptides such as polymerized British amyloidosis (ABri)-related peptide (pBri)57 are used as immunogens.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [57]
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Self-citationHovakimyan, A., Antonyan, T., Shabestari, S. K., Svystun, O., Chailyan, G., Coburn, M., Carlen-Jones, W., Petrushina, I., Chadarevian, J. P., Zagorski, K., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-51809-2 · Cited by 26 · see citing works
Boutajangout, A., Lindberg, H., Awwad, A., Paul, A., Baitalmal, R., Almokyad, I. K., Höidén‐Guthenberg, I., Gunneriusson, E., Frejd, F. Y., Härd, T., et al. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00064 · Cited by 25 · see citing works
Herline, K., Prelli, F., Mehta, P. D., MacMurray, C., Goñi, F., & Wısnıewskı, T. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0384-9 · Cited by 24 · see citing works
Self-citationGüell‐Bosch, J., Lope‐Piedrafita, S., Esquerda‐Canals, G., Montoliu‐Gaya, L., & Villegas, S. (2020) · NMR in Biomedicine · doi:10.1002/nbm.4263 · Cited by 21 · see citing works
Goñi, F., Martá-Ariza, M., Herline, K., Peyser, D. K., Boutajangout, A., Mehta, P. D., Drummond, E., Prelli, F. C., & Wısnıewskı, T. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0337-3 · Cited by 20 · see citing works
Self-citationFuture horizons in Alzheimer's disease research
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Puangmalai, N., Bhatt, N. N., Bittar, A., Jerez, C., Shchankin, N., & Kayed, R. (2023) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2023.102562 · Cited by 17 · see citing works
Goñi, F., Martá-Ariza, M., Peyser, D. K., Herline, K., & Wısnıewskı, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-10393-z · Cited by 16 · see citing works
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A critical overview of therapeutic strategy and advancement for Alzheimer's disease treatment
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Alzheimer’s disease and immunotherapy: what is wrong with clinical trials?
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Scholtzova, H., Do, E., Dhakal, S., Sun, Y., Liu, S., Mehta, P. D., & Wısnıewskı, T. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1967-16.2017 · Cited by 6 · see citing works
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Self-citationTransmissible Spongiform Encephalopathies
Wısnıewskı, T., & Goñi, F. (2016) · Springer eBooks · doi:10.1007/978-3-319-33189-8_7 · Cited by 5 · see citing works
Self-citationNovel immunological approaches for the treatment of Alzheimer's disease.
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The Role of T Cells in Alzheimer's Disease Pathogenesis
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Tau-Centric Therapies for Treating Alzheimer’s Disease
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Self-citationHétérogénéité de la réactivité astrocytaire dans la maladie d'Alzheimer
Guillemaud, O. (2020) · theses.fr (ABES) · doi:10.70675/038d98c5z55ccz4754z9af9z417e3826d282
- Authors
- Goñi, F., Herline, K., Peyser, D., Wong, K., Ji, Y., Sun, Y., Mehta, P., & Wisniewski, T.
- Affiliations
- New York University (US)
- Tianjin Huanhu Hospital (CN)
- Venue
- Journal of Neuroinflammation
- Published
- 2013-12
- Volume
- 10
- Issue
- 1
- Pages
- 150-150
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC3878790
- OpenAlex
- W2001271051
- Cited by
- 43
- References
- 66
- Citations by year
- 2023: 5 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 5
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG20245, AG08051)
- National Institute on Aging (AG20245, P30AG008051, AG 08051, R01AG020245)
- National Institute of Neurological Disorders and Stroke (NS073502, R01NS073502)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, immunomodulation, amyloid-beta, tau pathology, immunization, peptide oligomerization, 3xTg-AD mice, cerebral amyloid angiopathy, vascular amyloid deposits, humoral immune response, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Humans, Immunization, Luminescent Measurements, Mice, Transgenic, Blotting, Western, Amyloid beta-Peptides, tau Proteins, Protein Structure, Secondary, Molecular Mimicry, Mice, Amyloidogenic Proteins
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