{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:34:36Z","timestamp":1765344876281,"version":"3.46.0"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objectives: Alzheimer\u2019s disease (AD) and other dementias represent a growing public health concern, highlighting the need for reliable biomarkers for early diagnosis and treatment monitoring. This study evaluated the potential utility of BIN1 and TOMM40 genotyping in diagnosing mild cognitive impairment (MCI) and early-stage dementia. Methods: The BIN1 rs744373 and TOMM40 rs2075650 polymorphisms were genotyped in a cohort of 105 individuals diagnosed with MCI or dementia and in 164 cognitively healthy controls. Genotype distributions were compared between the groups, and the potential role of these variants in diagnostic assessment was explored. Results: A significantly higher frequency of the TOMM40 rs2075650 GG genotype was observed in patients with AD compared with cognitively healthy controls. In contrast, no statistically significant differences in genotype distribution were found among individuals with mild MCI, vascular dementia, or mixed dementia. Furthermore, the distribution of BIN1 rs744373 alleles did not differ significantly across the analyzed groups. Conclusions: Data on the effects of BIN1 rs744373 and TOMM40 rs2075650 polymorphisms in MCI and dementia remain limited and inconsistent. In our study, significant differences were observed only for the TOMM40 rs2075650 GG genotype and G allele, which were more frequent in Alzheimer\u2019s disease patients than in controls. No significant associations were found for MCI, vascular dementia, or mixed dementia, nor for the BIN1 rs744373 polymorphism. These results suggest that TOMM40 rs2075650 genotyping may serve as an additional marker for assessing AD risk.<\/jats:p>","DOI":"10.3390\/genes16121469","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"1469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Diagnostic Reliability of BIN1 and TOMM40 Genotyping in Assessing Dementia Risk"],"prefix":"10.3390","volume":"16","author":[{"given":"Marta","family":"Machowska","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy","family":"Leszek","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Miko\u0142ajczyk-Tarnawa","sequence":"additional","affiliation":[{"name":"Screening of Biological Activity Assays and Collection of Biological Material Laboratory, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystyna","family":"G\u0142owacka","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"El\u017cbieta","family":"Trypka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2789-5911","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"R\u0105pa\u0142a","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, T. Marciniak Lower Silesian Specialist Hospital, 54-049 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janusz","family":"Piechota","sequence":"additional","affiliation":[{"name":"Amplicon Ltd., 54-413 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-2300","authenticated-orcid":false,"given":"Anna","family":"Wiela-Hoje\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2024). 2024 Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 20, 3708\u20133821.","DOI":"10.1002\/alz.13809"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.3233\/JAD-240260","article-title":"Potential Biomarkers in Cerebrospinal Fluid and Plasma for Dementia","volume":"100","author":"He","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"909","DOI":"10.2217\/bmm.13.107","article-title":"The First Genetic Biomarker for Dementia with Lewy Bodies","volume":"7","author":"Beyer","year":"2013","journal-title":"Biomark. Med."},{"key":"ref_4","first-page":"2948","article-title":"BIN1 Regulates BACE1 Intracellular Trafficking and Amyloid-\u03b2 Production","volume":"25","author":"Miyagawa","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13024-022-00535-x","article-title":"BIN1 Is a Key Regulator of Proinflammatory and Neurodegeneration-Related Activation in Microglia","volume":"17","author":"Sudwarts","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Malvaso, A., Gatti, A., Negro, G., Calatozzolo, C., Medici, V., and Poloni, T.E. (2023). Microglial Senescence and Activation in Healthy Aging and Alzheimer\u2019s Disease: Systematic Review and Neuropathological Scoring. Cells, 12.","DOI":"10.37766\/inplasy2023.11.0064"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.3233\/JAD-132450","article-title":"Bridging Integrator 1 (BIN1) Protein Expression Increases in the Alzheimer\u2019s Disease Brain and Correlates with Neurofibrillary Tangle Pathology","volume":"42","author":"Holler","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/bpa.12687","article-title":"Aberrant Accrual of BIN1 near Alzheimer\u2019s Disease Amyloid Deposits in Transgenic Models","volume":"29","author":"Andrew","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/alz.12371","article-title":"The BIN1 rs744373 Alzheimer\u2019s Disease Risk SNP Is Associated with Faster A\u03b2-Associated Tau Accumulation and Cognitive Decline","volume":"18","author":"Franzmeier","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1038\/npp.2015.30","article-title":"Bridging Integrator 1 (BIN1) Genotype Effects on Working Memory, Hippocampal Volume, and Functional Connectivity in Young Healthy Individuals","volume":"40","author":"Zhang","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1038\/s41467-019-09564-5","article-title":"The BIN1 rs744373 SNP Is Associated with Increased Tau-PET Levels and Impaired Memory","volume":"10","author":"Franzmeier","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1093\/emboj\/cdg229","article-title":"Tom40, the Import Channel of the Mitochondrial Outer Membrane, Plays an Active Role in Sorting Imported Proteins","volume":"22","author":"Gabriel","year":"2003","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102056","DOI":"10.1016\/j.molmet.2024.102056","article-title":"TOMM40 Regulates Hepatocellular and Plasma Lipid Metabolism via an LXR-Dependent Pathway","volume":"90","author":"Yang","year":"2024","journal-title":"Mol. Metab."},{"key":"ref_14","first-page":"12","article-title":"The Broad Impact of TOM40 on Neurodegenerative Diseases in Aging","volume":"1","author":"Gottschalk","year":"2014","journal-title":"J. Parkinsons Dis. Alzheimers Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.neulet.2016.05.050","article-title":"The TOMM40 Gene rs2075650 Polymorphism Contributes to Alzheimer\u2019s Disease in Caucasian and Asian Populations","volume":"628","author":"Huang","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3233\/JAD-2010-1428","article-title":"Trial News: Woes, New Approaches","volume":"22","author":"Landhuis","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1017\/S1041610224000942","article-title":"Global Dementia Strategy: Current Stage and Challenges","volume":"36","author":"Urbina","year":"2024","journal-title":"Int. Psychogeriatr."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Firdaus, Z., and Li, X. (2024). Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042320"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102852","DOI":"10.1016\/j.arr.2025.102852","article-title":"Meta-analyses of personality change from the preclinical to the clinical stages of dementia","volume":"112","author":"Terracciano","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15132","DOI":"10.18632\/oncotarget.23738","article-title":"The Genes Associated with Early-Onset Alzheimer\u2019s Disease","volume":"9","author":"Dai","year":"2017","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3233\/JAD-190193","article-title":"Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer\u2019s Disease Before 51 Years","volume":"71","author":"Lacour","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bruno, F., Aceto, M.A., Paparazzo, E., Arcuri, D., Vozzo, F., Mirante, S., Greco, B.M., Serra Cassano, T., Abondio, P., and Canterini, S. (2025). Genetic variability in ADAM17\/TACE is associated with sporadic Alzheimer\u2019s disease risk, neuropsychiatric symptoms and cognitive performance on the Rey Auditory Verbal Learning and Clock Drawing Tests. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0309631"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.32598\/CJNS.9.33.6","article-title":"The Relationship Between Bridging Integrator 1 Gene Polymorphism and Susceptibility to Alzheimer\u2019s Disease","volume":"9","author":"Saberi","year":"2023","journal-title":"Casp. J. Neurol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neulet.2013.02.075","article-title":"BIN1 Gene rs744373 Polymorphism Contributes to Alzheimer\u2019s Disease in East Asian Population","volume":"544","author":"Liu","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_25","first-page":"7","article-title":"A comprehensive review on novel opportunities for Alzheimer therapy by targeting BIN1","volume":"26","author":"Mostafa","year":"2025","journal-title":"Egypt J. Med. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/YPG.0000000000000071","article-title":"Common Variants at BIN1 Are Associated with Sporadic Alzheimer\u2019s Disease in the Han Chinese Population","volume":"25","author":"Li","year":"2015","journal-title":"Psychiatr. Genet."},{"key":"ref_27","first-page":"e12227","article-title":"Lack of Association Between Bridging Integrator 1 (BIN1) rs744373 Polymorphism and Tau-PET Load in Cognitively Intact Older Adults","volume":"8","author":"Schaeverbeke","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref_28","first-page":"681","article-title":"Monta\u00f1\u00e9s; et al. Analysis of Cognitive Performance and Polymorphisms of SORL1, PVRL2, CR1, TOMM40, APOE, PICALM, GWAS_14q, CLU, and BIN1 in Patients with Mild Cognitive Impairment and Cognitively Healthy Controls","volume":"36","author":"Estrada","year":"2021","journal-title":"Neurologia (Engl. Ed.)"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cachide, M., Carvalho, L., Rosa, I.M., Wiltfang, J., Henriques, A.G., and da Cruz e Silva, O.A.B. (2022). BIN1 rs744373 SNP and APOE Alleles Specifically Associate to Common Diseases. Front. Dement., 1.","DOI":"10.3389\/frdem.2022.1001113"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.12659\/MSM.895622","article-title":"Associations Between Genetic Variants in 19p13 and 19q13 Regions and Susceptibility to Alzheimer Disease: A Meta-Analysis","volume":"22","author":"Bao","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neurobiolaging.2021.12.013","article-title":"Association and Interaction of TOMM40 and PVRL2 with Plasma Amyloid-\u03b2 and Alzheimer\u2019s Disease Among Chinese Older Adults: A Population-Based Study","volume":"113","author":"Liang","year":"2022","journal-title":"Neurobiol. Aging"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, Y.-C., Chang, S.-C., Lee, Y.-S., Ho, W.-M., Huang, Y.-H., Wu, Y.-Y., Chu, Y.-C., Wu, K.-H., Wei, L.-S., and Wang, H.-L. (2023). TOMM40 Genetic Variants Cause Neuroinflammation in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044085"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/WAD.0000000000000142","article-title":"Association Analysis of Polymorphisms in TOMM40, CR1, PVRL2, SORL1, PICALM, and 14q32.13 Regions in Colombian Alzheimer Disease Patients","volume":"30","author":"Morales","year":"2016","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gui, W., Qiu, C., Shao, Q., and Li, J. (2021). Associations of Vascular Risk Factors, APOE and TOMM40 Polymorphisms with Cognitive Function in Dementia-Free Chinese Older Adults: A Community-Based Study. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.617773"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.jalz.2018.06.269","article-title":"The TOMM40 Gene rs2075650 Polymorphism Predicts the 2-Year Outcome of Amnestic Mild Cognitive Impairment in Chinese Han Population","volume":"14","author":"Zhao","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.jalz.2015.06.884","article-title":"TOMM40\/APOE Variation and Age of Onset of Mild Cognitive Impairment and Dementia in a Prospective, Longitudinal Study","volume":"11","author":"Lutz","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2107.e7","DOI":"10.1016\/j.neurobiolaging.2011.05.023","article-title":"Genetic Variation in APOE Cluster Region and Alzheimer\u2019s Disease Risk","volume":"32","author":"Cervantes","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/mp.2012.159","article-title":"A Genome-Wide Association Study Implicates the APOE Locus in Nonpathological Cognitive Ageing","volume":"19","author":"Davies","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35207","DOI":"10.18632\/oncotarget.26184","article-title":"Biothiols and Oxidative Stress Markers and Polymorphisms of TOMM40 and APOC1 Genes in Alzheimer\u2019s Disease Patients","volume":"9","author":"Prendecki","year":"2018","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.3233\/JAD-230066","article-title":"TOMM40 \u2019523 genotype distinguishes patterns of cognitive improvement for executive function in APOE \u025b3 homozygotes","volume":"95","author":"Watts","year":"2023","journal-title":"J. Alzheimers Dis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/12\/1469\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:31:58Z","timestamp":1765344718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/12\/1469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,8]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["genes16121469"],"URL":"https:\/\/doi.org\/10.3390\/genes16121469","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2025,12,8]]}}}