{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:08:00Z","timestamp":1789024080547,"version":"build-2803163510"},"reference-count":175,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0 http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:p>\n                    Accumulation of amyloid-beta is highly important in the development of Alzheimer\u2019s disease. Given the limitations of the amyloid cascade hypothesis and the repeated clinical failures of anti-amyloid-beta therapies, researchers are increasingly exploring the infection hypothesis. This review explores the dual behaviors of amyloid-beta in Alzheimer\u2019s disease, with a particular focus on its protective role against infection by microorganisms and its complicated connections with innate immune system. This new opinion holds that amyloid-beta can play an antimicrobial peptide role. During microbial invasion, its original role is to protect neural tissue, but prolonged accumulation leads to chronic deposition and involvement in pathological processes. Evidence from\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    experiments, animal models, and clinical studies indicates that amyloid-beta may possess antiviral and antibacterial properties, particularly against infections such as herpes simplex virus, human immunodeficiency virus, and\n                    <jats:italic toggle=\"yes\">Porphyromonas gingivalis<\/jats:italic>\n                    . However, excessive accumulation of amyloid beta triggers a neuroinflammatory cascade that impairs neuronal regeneration and cognitive function. Despite substantial research into Alzheimer\u2019s disease, current treatments have not yielded significant clinical benefits. Although monoclonal antibodies such as\n                    <jats:italic toggle=\"yes\">Aducanumab<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Lecanemab<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Donanemab<\/jats:italic>\n                    have been approved for marketing, their strict indications and high costs pose challenges for widespread promotion. The infection hypothesis of amyloid-beta has spurred clinical trials investigating vaccines targeting specific pathogens to assess their potential in preventing or treating Alzheimer\u2019s disease. This highlights the need for further exploring the multifaceted role of amyloid-beta in Alzheimer\u2019s disease. In addition, microbial infections can also trigger or regulate genetic and epigenetic factors, accelerating amyloid beta deposition. Among them, the apolipoprotein E epsilon 4 allele is the strongest genetic risk factor for Alzheimer\u2019s disease, as it exacerbates the accumulation of amyloid beta and promotes neuroinflammation. Strategies targeting epigenetic regulation may provide novel approaches to inhibit Alzheimer\u2019s disease pathology. This review also integrates various technologies such as genomics, proteomics, and metabolomics. This provides a broader system-level understanding of the risk gene loci, protein interaction networks, and metabolic changes associated with amyloid beta under the influence of microbial infections. Such techniques may lead to the identification of new molecular targets, the development of individualized treatment strategies, and the creation of early biomarkers for use in clinical research. In conclusion, this review suggests that amyloid-beta is not merely a pathological by-product but an environmentally responsive molecule with dual functions. A deeper understanding of the dynamic regulation of amyloid-beta, considering infection status and disease stage, can provide new directions for treatment strategies aimed at the prevention and treatment of Alzheimer\u2019s disease.\n                  <\/jats:p>\n                  <jats:p\/>","DOI":"10.4103\/nrr.nrr-d-25-00872","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T05:00:19Z","timestamp":1770008419000},"page":"5171-5180","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of the dual role of amyloid-beta in Alzheimer\u2019s disease through multi-omics integration"],"prefix":"10.4103","volume":"21","author":[{"given":"Jingwen","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Hospital of China Medical University, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luying","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weishuang","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hefei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Hospital of China Medical University, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1330-6298","authenticated-orcid":false,"given":"Yanzhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning Province, 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