{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:02:22Z","timestamp":1788627742692,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["grant agreement \u2116 075-15-2020-795, state contract \u2116 13.1902.21.0027 of 29.09.2020 unique project ID: RF-190220X0027"],"award-info":[{"award-number":["grant agreement \u2116 075-15-2020-795, state contract \u2116 13.1902.21.0027 of 29.09.2020 unique project ID: RF-190220X0027"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia among the elderly. Neuropathologically, AD is characterized by the deposition of a 39- to 42-amino acid long \u03b2-amyloid (A\u03b2) peptide in the form of senile plaques. Several post-translational modifications (PTMs) in the N-terminal domain have been shown to increase the aggregation and cytotoxicity of A\u03b2, and specific A\u03b2 proteoforms (e.g., A\u03b2 with isomerized D7 (isoD7-A\u03b2)) are abundant in the senile plaques of AD patients. Animal models are indispensable tools for the study of disease pathogenesis, as well as preclinical testing. In the presented work, the accumulation dynamics of A\u03b2 proteoforms in the brain of one of the most widely used amyloid-based mouse models (the 5xFAD line) was monitored. Mass spectrometry (MS) approaches, based on ion mobility separation and the characteristic fragment ion formation, were applied. The results indicated a gradual increase in the A\u03b2 fraction of isoD7-A\u03b2, starting from approximately 8% at 7 months to approximately 30% by 23 months of age. Other specific PTMs, in particular, pyroglutamylation, deamidation, and oxidation, as well as phosphorylation, were also monitored. The results for mice of different ages demonstrated that the accumulation of A\u03b2 proteoforms correlate with the formation of A\u03b2 deposits. Although the mouse model cannot be a complete analogue of the processes occurring in the human brain in AD, and several of the observed parameters differ significantly from human values supposedly due to the limited lifespan of the model animals, this dynamic study provides evidence on at least one of the possible mechanisms that can trigger amyloidosis in AD, i.e., the hypothesis on the relationship between the accumulation of isoD7-A\u03b2 and the progression of AD-like pathology.<\/jats:p>","DOI":"10.3390\/ijms23010027","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T09:50:43Z","timestamp":1640080243000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Dynamics of \u03b2-Amyloid Proteoforms Accumulation in the Brain of a 5xFAD Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1515-9447","authenticated-orcid":false,"given":"Anna E.","family":"Bugrova","sequence":"first","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6513-8009","authenticated-orcid":false,"given":"Polina A.","family":"Strelnikova","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119334 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-7449","authenticated-orcid":false,"given":"Maria I.","family":"Indeykina","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119334 Moscow, Russia"},{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2238-3458","authenticated-orcid":false,"given":"Alexey S.","family":"Kononikhin","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"},{"name":"Skolkovo Institute of Science and Technology, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia V.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Brzhozovskiy","sequence":"additional","affiliation":[{"name":"Skolkovo Institute of Science and Technology, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny P.","family":"Barykin","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9622-3457","authenticated-orcid":false,"given":"Stanislav I.","family":"Pekov","sequence":"additional","affiliation":[{"name":"Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia"},{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"},{"name":"Skolkovo Institute of Science and Technology, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria S.","family":"Gavrish","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey A.","family":"Babaev","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-1799","authenticated-orcid":false,"given":"Anna M.","family":"Kosyreva","sequence":"additional","affiliation":[{"name":"Research Institute of Human Morphology, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Y.","family":"Morozova","sequence":"additional","affiliation":[{"name":"Department of Basic and Applied Neurobiology, Federal Medical Research Center for Psychiatry and Narcology, 119034 Moscow, Russia"},{"name":"Mental-Health Clinic No. 1 Named after N.A. 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