{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:39:27Z","timestamp":1793320767744,"version":"4.5.0"},"reference-count":271,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State assignment \u201cCreation of a radiopharmaceutical drug for the diagnosis of Alzheimer\u2019s disease using the tetrapeptide HAEE as a vector molecule\u201d","award":["EGISU NIOKTR 1024110600012-8-3.2.25;3.2.26;3.2.12"],"award-info":[{"award-number":["EGISU NIOKTR 1024110600012-8-3.2.25;3.2.26;3.2.12"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common cause of dementia worldwide, and there are still no strategies to slow or prevent its clinical progression. Significant financial and research resources have been invested into studying the pathology of AD. However, its pathogenesis is not fully understood. This review provides a comprehensive analysis of current understanding of AD pathogenesis, including classical hypotheses (amyloid cascade, tau pathology, neuroinflammation, oxidative stress), emerging mechanisms (cellular senescence, endoplasmic reticulum stress, ubiquitin-proteasome system dysfunction), and alternative mechanisms (cholinergic dysfunction, glutamate excitotoxicity, disruption of the microbiota\u2013gut\u2013brain axis, and autophagy). Schematic illustrations summarize the relationships between the hypotheses and their role in the pathogenesis of AD. Particular attention is paid to the systematization of promising biological targets and the analysis of modern ligands of various nature, including small molecules, peptides, antibodies and their fragments, natural compounds, as well as innovative hybrid and multifunctional structures. A separate section is devoted to radiopharmaceuticals for PET imaging (Florbetaben, Flortaucipir, etc.) and promising therapeutic agents. Thus, in this review we (1) systematize modern concepts of AD pathogenesis, including classical, emerging mechanisms and alternative hypotheses; (2) conduct a comparative analysis of ligand classes (small molecules, peptides, antibodies, etc.) and their therapeutic potential; and (3) discuss the clinical prospects of radiopharmaceuticals for PET imaging and targeted therapy. The work provides a comprehensive analysis of modern approaches, which can help in the development of more effective drugs against AD.<\/jats:p>","DOI":"10.3390\/ijms26199444","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:54:48Z","timestamp":1759229688000},"page":"9444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Alzheimer\u2019s Disease: From Molecular Mechanisms to Promising Therapeutic Strategies"],"prefix":"10.3390","volume":"26","author":[{"given":"Anna V.","family":"Ivanova","sequence":"first","affiliation":[{"name":"Department of Medical Nanobiotechnology, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra D.","family":"Kutuzova","sequence":"additional","affiliation":[{"name":"Department of Medical Nanobiotechnology, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7092-1777","authenticated-orcid":false,"given":"Ilia A.","family":"Kuzmichev","sequence":"additional","affiliation":[{"name":"Department of Medical Nanobiotechnology, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-9201","authenticated-orcid":false,"given":"Maxim A.","family":"Abakumov","sequence":"additional","affiliation":[{"name":"Department of Medical Nanobiotechnology, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tackenberg, C., Kulic, L., and Nitsch, R.M. (2020). Familial Alzheimer\u2019s Disease Mutations at Position 22 of the Amyloid \u03b2-Peptide Sequence Differentially Affect Synaptic Loss, Tau Phosphorylation and Neuronal Cell Death in an Ex Vivo System. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239584"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6701","DOI":"10.1039\/C4CS00026A","article-title":"Metal Complexes Designed to Bind to Amyloid-\u03b2 for the Diagnosis and Treatment of Alzheimer\u2019s Disease","volume":"43","author":"Hayne","year":"2014","journal-title":"Chem. Soc. 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