{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:35:03Z","timestamp":1787726103315,"version":"build-2784847793"},"reference-count":81,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01-AG020241"],"award-info":[{"award-number":["R01-AG020241"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-translationally modified N-terminally truncated amyloid beta peptide with a cyclized form of glutamate at position 3 (pE3A\u03b2) is a highly pathogenic molecule with increased neurotoxicity and propensity for aggregation. In the brains of Alzheimer\u2019s Disease (AD) cases, pE3A\u03b2 represents a major constituent of the amyloid plaque. The data show that pE3A\u03b2 formation is increased at early pre-symptomatic disease stages, while tau phosphorylation and aggregation mostly occur at later stages of the disease. This suggests that pE3A\u03b2 accumulation may be an early event in the disease pathogenesis and can be prophylactically targeted to prevent the onset of AD. The vaccine (AV-1986R\/A) was generated by chemically conjugating the pE3A\u03b23-11 fragment to our universal immunogenic vaccine platform MultiTEP, then formulated in AdvaxCpG adjuvant. AV-1986R\/A showed high immunogenicity and selectivity, with endpoint titers in the range of 105\u2013106 against pE3A\u03b2 and 103\u2013104 against the full-sized peptide in the 5XFAD AD mouse model. The vaccination showed efficient clearance of the pathology, including non-pyroglutamate-modified plaques, from the mice brains. AV-1986R\/A is a novel promising candidate for the immunoprevention of AD. It is the first late preclinical candidate which selectively targets a pathology-specific form of amyloid with minimal immunoreactivity against the full-size peptide. Successful translation into clinic may offer a new avenue for the prevention of AD via vaccination of cognitively unimpaired individuals at risk of disease.<\/jats:p>","DOI":"10.3390\/ijms24129797","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T02:57:30Z","timestamp":1686020250000},"page":"9797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel Vaccine against Pathological Pyroglutamate-Modified Amyloid Beta for Prevention of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Karen","family":"Zagorski","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"King","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular 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