{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:05:31Z","timestamp":1784293531637,"version":"3.55.0"},"reference-count":99,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) is a heterogeneous disorder with multiple patterns of clinical manifestations. Recently, due to the advance of linkage studies, next\u2010generation sequencing and genome\u2010wide association studies, a large number of putative risk genes for AD have been identified using acquired genome mega data. The genetic association between three causal genes, including amyloid precursor protein, presenilin1, and presenilin2 in\u00a0early\u2010onset AD (EOAD), was discovered over the past few decades. These discoveries showed that there should be additional genetic risk factors for both EOAD and late\u2010onset AD (LOAD) to help fully explain the leading molecular mechanisms in a single pathophysiological entity. This\u00a0study reviews the clinical features and genetic etiology of LOAD and discusses a variety of AD\u2010mediated genes that are involved in cholesterol and lipid metabolism, endocytosis, and immune response according to their mutations for more efficient selection of functional candidate genes for LOAD. New mechanisms and pathways have been identified as a result.<\/jats:p>","DOI":"10.1002\/jcp.28372","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T00:41:29Z","timestamp":1550709689000},"page":"16873-16884","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic discoveries and advances in late\u2010onset Alzheimer\u2019s disease"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0790-1317","authenticated-orcid":false,"given":"Maryam","family":"Rezazadeh","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine, Tabriz University of Medical Sciences Tabriz Iran"},{"name":"Division of Medical Genetics Tabriz Children\u2019s Hospital, Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Hosseinzadeh","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Science, Yazd University Yazd Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Moradi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine, Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behnaz","family":"Salek Esfahani","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine, Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Talebian","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine, Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaho","family":"Parvin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine, Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2613-3421","authenticated-orcid":false,"given":"Jalal","family":"Gharesouran","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine, Tabriz University of Medical Sciences Tabriz Iran"},{"name":"Division of Medical Genetics Tabriz Children\u2019s Hospital, Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"e_1_2_13_1_2_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-110356"},{"key":"e_1_2_13_1_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb03138.x"},{"key":"e_1_2_13_1_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0891988710383571"},{"key":"e_1_2_13_1_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31816b64dc"},{"key":"e_1_2_13_1_6_1","volume-title":"Alzheimer disease overview","author":"Bird T. D.","year":"2015"},{"issue":"2","key":"e_1_2_13_1_7_1","first-page":"2393","article-title":"Alzheimer\u2019s disease and other dementias","volume":"16","author":"Bird T. D.","year":"2005","journal-title":"Harrisons Principles of Internal Medicine"},{"key":"e_1_2_13_1_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg007"},{"key":"e_1_2_13_1_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.9.1307"},{"key":"e_1_2_13_1_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890802186905"},{"key":"e_1_2_13_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.063"},{"key":"e_1_2_13_1_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002156"},{"key":"e_1_2_13_1_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05433.x"},{"key":"e_1_2_13_1_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179573517709278"},{"key":"e_1_2_13_1_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00124"},{"key":"e_1_2_13_1_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq160"},{"key":"e_1_2_13_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00127-7"},{"key":"e_1_2_13_1_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205011310030010"},{"key":"e_1_2_13_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.10.022"},{"key":"e_1_2_13_1_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.117135"},{"key":"e_1_2_13_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.08.014"},{"key":"e_1_2_13_1_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318065c495"},{"key":"e_1_2_13_1_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1784"},{"key":"e_1_2_13_1_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MXE.0000430777.29752.3a"},{"key":"e_1_2_13_1_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-014-0377-5"},{"key":"e_1_2_13_1_26_1","doi-asserted-by":"publisher","DOI":"10.2298\/GENSR1302503G"},{"key":"e_1_2_13_1_27_1","first-page":"2894","article-title":"A pilot study of gene\/gene and gene\/environment interactions in Alzheimer disease","volume":"2010","author":"Ghebranious N.","year":"2010","journal-title":"Clinical Medicine and Research"},{"key":"e_1_2_13_1_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066664"},{"key":"e_1_2_13_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.04.014"},{"key":"e_1_2_13_1_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0295-9"},{"key":"e_1_2_13_1_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1245-5"},{"key":"e_1_2_13_1_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2007.00694.x"},{"key":"e_1_2_13_1_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.440"},{"key":"e_1_2_13_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.11.021"},{"key":"e_1_2_13_1_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.2628"},{"key":"e_1_2_13_1_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.803"},{"issue":"5","key":"e_1_2_13_1_37_1","first-page":"627","article-title":"Molecular and cellular mechanisms of apolipoprotein E4 neurotoxicity and potential therapeutic strategies","volume":"9","author":"Huang Y.","year":"2006","journal-title":"Current Opinion in Drug Discovery and Development"},{"key":"e_1_2_13_1_38_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S11718"},{"key":"e_1_2_13_1_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.006"},{"key":"e_1_2_13_1_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050976"},{"key":"e_1_2_13_1_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_2_13_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.11.021"},{"key":"e_1_2_13_1_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.163"},{"key":"e_1_2_13_1_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl280"},{"key":"e_1_2_13_1_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.11.1737"},{"key":"e_1_2_13_1_46_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-09-0987"},{"key":"e_1_2_13_1_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn960"},{"key":"e_1_2_13_1_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00570-0"},{"key":"e_1_2_13_1_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2009.04.009"},{"key":"e_1_2_13_1_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_13_1_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4580-03.2004"},{"key":"e_1_2_13_1_52_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S74042"},{"key":"e_1_2_13_1_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-013-1391-2"},{"key":"e_1_2_13_1_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313768111"},{"key":"e_1_2_13_1_55_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.29937"},{"key":"e_1_2_13_1_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.12.003"},{"key":"e_1_2_13_1_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.11.002"},{"key":"e_1_2_13_1_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.09.050"},{"key":"e_1_2_13_1_59_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.22"},{"key":"e_1_2_13_1_60_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0887"},{"key":"e_1_2_13_1_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1224-13.2013"},{"key":"e_1_2_13_1_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.09.008"},{"key":"e_1_2_13_1_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.3114pe10"},{"key":"e_1_2_13_1_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.6.2785"},{"key":"e_1_2_13_1_65_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_13_1_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2017.08.009"},{"issue":"14","key":"e_1_2_13_1_67_1","first-page":"2948","article-title":"BIN1 regulates BACE1 intracellular trafficking and amyloid\u2010\u03b2 production","volume":"25","author":"Miyagawa T.","year":"2016","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_13_1_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-6-52"},{"key":"e_1_2_13_1_69_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/929042"},{"issue":"2","key":"e_1_2_13_1_70_1","first-page":"111","article-title":"Association of CCR2 gene but not CCR5 gene polymorphisms with Alzheimer\u2019s disease","volume":"22","author":"Mohaddes Ardebili S. M.","year":"2011","journal-title":"Journal of Sciences, Islamic Republic of Iran"},{"issue":"8","key":"e_1_2_13_1_71_1","first-page":"1006","article-title":"Genetic association of TNF\u2010\u03b1\u2010308 G\/A and\u2010863 C\/A polymorphisms with late onset Alzheimer\u2019s disease in Azeri Turk population of Iran","volume":"16","author":"Mohaddes Ardebili S. M.","year":"2011","journal-title":"Journal of Research in Medical Sciences"},{"key":"e_1_2_13_1_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.01.008"},{"key":"e_1_2_13_1_73_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2017-0036"},{"key":"e_1_2_13_1_74_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200808080"},{"key":"e_1_2_13_1_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.801"},{"key":"e_1_2_13_1_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.257"},{"key":"e_1_2_13_1_77_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4081-14.2015"},{"key":"e_1_2_13_1_78_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050151"},{"key":"e_1_2_13_1_79_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.6.2575"},{"key":"e_1_2_13_1_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-008-9626-8"},{"key":"e_1_2_13_1_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.10.011"},{"key":"e_1_2_13_1_82_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1146-08.2008"},{"key":"e_1_2_13_1_83_1","doi-asserted-by":"publisher","DOI":"10.1177\/0891988705281883"},{"key":"e_1_2_13_1_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10153"},{"key":"e_1_2_13_1_85_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.196"},{"key":"e_1_2_13_1_86_1","doi-asserted-by":"publisher","DOI":"10.2298\/GENSR1402437S"},{"key":"e_1_2_13_1_87_1","doi-asserted-by":"publisher","DOI":"10.3906\/sag-1406-64"},{"key":"e_1_2_13_1_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3246"},{"key":"e_1_2_13_1_89_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.6.1541"},{"key":"e_1_2_13_1_90_1","first-page":"13","article-title":"Synapses, synaptic activity and intraneuronal A\u03b2 in Alzheimer\u2019s disease","volume":"2","author":"Tampellini D.","year":"2010","journal-title":"Frontiers in Aging Neuroscience"},{"key":"e_1_2_13_1_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(96)00119-9"},{"key":"e_1_2_13_1_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2015.10.004"},{"key":"e_1_2_13_1_93_1","doi-asserted-by":"publisher","DOI":"10.3109\/01677063.2011.620191"},{"key":"e_1_2_13_1_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.09.006"},{"key":"e_1_2_13_1_95_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-111844"},{"key":"e_1_2_13_1_96_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8742-5"},{"key":"e_1_2_13_1_97_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"e_1_2_13_1_98_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4396-06.2007"},{"key":"e_1_2_13_1_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4025"},{"key":"e_1_2_13_1_100_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8723-8"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.28372","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.28372","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.28372","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.28372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:44:10Z","timestamp":1784292250000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.28372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,20]]},"references-count":99,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/jcp.28372"],"URL":"https:\/\/doi.org\/10.1002\/jcp.28372","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,20]]},"assertion":[{"value":"2018-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}