{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:19:43Z","timestamp":1789589983201,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":141,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["54\/8\/GER\/2019-NCD-II"],"award-info":[{"award-number":["54\/8\/GER\/2019-NCD-II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brain\u2010derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) are key regulators of neuronal function and cognitive health. Genetic variations in these genes, particularly nonsynonymous single\u2010nucleotide polymorphisms (nsSNPs), have been linked to Alzheimer\u2019s disease (AD). This study employs a computational approach to predict the potential functional impacts of nsSNPs in BDNF and APOE to explore their contributions to AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 3590 BDNF and 27,830 APOE SNPs were retrieved from the dbSNP database. Following quality filtering of coding region localization and minor allele frequency (\u2265\u20090.001), 33 BDNF nsSNPs and 95 APOE nsSNPs underwent systematic analysis. Pathogenicity was assessed using SIFT and PolyPhen\u20102 algorithms, with functional impact evaluated via CADD scoring. Protein stability effects were predicted using MUpro and I\u2010Mutant tools, and posttranslational modifications were analyzed via a GPS prediction system. Secondary structure alterations were assessed using GOR4, and three\u2010dimensional structural models were generated through SWISS\u2010MODEL with Ramachandran plot validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three variants demonstrated concordant pathogenic predictions: rs1048218 (BDNF Q75H), rs7412 (APOE R176C), and rs769455 (APOE R163C). Protein stability analysis of these variants revealed consistent destabilization for rs1048218 (\n                      <jats:italic>\u0394\u0394<\/jats:italic>\n                      G: \u22121.001 to \u22122.08\u2009kcal\/mol) and rs7412 (\n                      <jats:italic>\u0394\u0394<\/jats:italic>\n                      G: \u22120.859 to \u22120.07\u2009kcal\/mol), whereas rs769455 showed conflicting predictions between algorithms. Posttranslational modification sites remained conserved across all the variants. Secondary structure analysis demonstrated minimal\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \u2010helix reduction (0.31%\u20130.81%) with compensatory random coil increases. Three\u2010dimensional modeling revealed preserved overall protein folds despite localized structural perturbations, with acceptable model quality metrics (MolProbity scores \u2264\u20091.39, Ramachandran favored regions &gt;91%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In silico analysis suggested that certain nsSNPs in BDNF and APOE may negatively affect protein function and stability, despite preserved structural and posttranslational features. These computational predictions need further experimental validation to better understand their roles in AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/bmri\/3806517","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T09:33:12Z","timestamp":1779442392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predictive Analysis of Brain\u2010Derived Neurotrophic Factor and Apolipoprotein E SNPs in Alzheimer\u2019s Pathogenesis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3451-0226","authenticated-orcid":false,"given":"Muralidhara Nitheesh","family":"Beliraya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-7165","authenticated-orcid":false,"given":"Sandeep","family":"Mallya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-4085","authenticated-orcid":false,"given":"Sudharshan","family":"Prabhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-024-01465-9"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00432-x"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/25424823251341870"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2022.105622"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2022.102575"},{"key":"e_1_2_11_6_2","article-title":"Genetic Interaction of APOE and BDNF is Associated With Changes in Cognitive Function Over 36 Months in Older Adults","volume":"17","author":"Pan G.","year":"2021","journal-title":"Alzheimer\u2032s & Dementia"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.1073905"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00574-4"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13091395"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00279-0"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2023.05.002"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.630502"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-24699-0"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae977"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad989"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20810"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki375"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.11.001"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-S1-S5"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.653267"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30412-9"},{"key":"e_1_2_11_26_2","article-title":"The Regulated Secretory Pathway and Human Disease: Insights From Gene Variants and Single Nucleotide Polymorphisms","volume":"4","author":"Lin W. 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