Abstract
Background: The hippocampus, entorhinal cortex, and fusiform gyrus are brain areas that deteriorate during early-stage Alzheimer’s disease (AD). The ApoE4 allele has been identified as a risk factor for AD development, is linked to an increase in the aggregation of amyloid β (Aβ) plaques in the brain, and is responsible for atrophy of the hippocampal area. However, to our knowledge, the rate of deterioration over time in individuals with AD, with or without the ApoE4 allele, has not been investigated.
Methods: In this study, we, for the first time, analyze atrophy in these brain structures in AD patients with and without the ApoE4 using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset.
Results: It was found that the rate of decrease in the volume of these brain areas over 12 months was related to the presence of ApoE4. Further, we found that neural atrophy was not different for female and male patients, unlike prior studies, suggesting that the presence of ApoE4 is not linked to the gender difference in AD.
Conclusion: Our results confirm and extend previous findings, showing that the ApoE4 allele gradually impacts brain regions impacted by AD.
[http://dx.doi.org/10.3233/JAD-2012-121408] [PMID: 23047370]
[http://dx.doi.org/10.18632/oncotarget.7797] [PMID: 26950278]
[http://dx.doi.org/10.1016/j.nbd.2014.07.011] [PMID: 25092575]
[http://dx.doi.org/10.1515/revneuro-2017-0036] [PMID: 28949931]
[http://dx.doi.org/10.1002/hipo.23304] [PMID: 33523577]
[http://dx.doi.org/10.1523/JNEUROSCI.1615-08.2008] [PMID: 18596169]
[http://dx.doi.org/10.3389/fnsys.2013.00045] [PMID: 24009563]
[http://dx.doi.org/10.1016/j.neuroimage.2021.118689] [PMID: 34742943]
[http://dx.doi.org/10.1101/2021.01.16.426538]
[http://dx.doi.org/10.1016/B0-12-227210-2/00232-6]
[http://dx.doi.org/10.1101/lm.1357309] [PMID: 19553381]
[http://dx.doi.org/10.1016/j.neures.2014.02.012] [PMID: 24642278]
[http://dx.doi.org/10.1002/hipo.23041] [PMID: 30311282]
[http://dx.doi.org/10.1111/bpa.13005] [PMID: 34269494]
[http://dx.doi.org/10.4103/0972-2327.104323] [PMID: 23349586]
[http://dx.doi.org/10.1016/j.neuroscience.2019.11.021] [PMID: 31812493]
[http://dx.doi.org/10.1515/revneuro-2016-0086] [PMID: 28422707]
[http://dx.doi.org/10.1016/j.neuron.2015.06.013] [PMID: 26139366]
[http://dx.doi.org/10.1007/s13205-022-03123-4] [PMID: 35116217]
[http://dx.doi.org/10.1016/j.expneurol.2021.113969] [PMID: 34973962]
[PMID: 24959551]
[http://dx.doi.org/10.1002/hipo.450010102] [PMID: 1669339]
[http://dx.doi.org/10.1136/jnnp.65.3.322] [PMID: 9728943]
[http://dx.doi.org/10.3389/fnagi.2020.00176] [PMID: 32714177]
[http://dx.doi.org/10.1109/RBME.2018.2796598] [PMID: 29994606]
[http://dx.doi.org/10.3389/fnins.2020.00804] [PMID: 32973425]
[http://dx.doi.org/10.1038/nn.3606] [PMID: 24362760]
[http://dx.doi.org/10.1016/j.pneurobio.2014.02.004] [PMID: 24548606]
[http://dx.doi.org/10.1016/j.arr.2021.101307] [PMID: 33621703]
[http://dx.doi.org/10.1002/1098-1063(2000)10:4<457::AIDHIPO12>3.0.CO;2-Z] [PMID: 10985285]
[http://dx.doi.org/10.1098/rstb.2012.0516] [PMID: 24366130]
[http://dx.doi.org/10.1016/j.neuroimage.2012.01.075] [PMID: 22289801]
[http://dx.doi.org/10.1186/s13148-020-00916-3] [PMID: 32854783]
[http://dx.doi.org/10.1016/j.celrep.2017.12.066] [PMID: 29346778]
[http://dx.doi.org/10.1007/s12035-018-1237-z] [PMID: 30032423]
[http://dx.doi.org/10.1073/pnas.0600549103] [PMID: 16567625]
[http://dx.doi.org/10.1016/j.nbd.2020.104784] [PMID: 32027932]
[http://dx.doi.org/10.1038/s43587-021-00073-z] [PMID: 35291561]
[http://dx.doi.org/10.1212/WNL.0000000000011270] [PMID: 33262228]
[http://dx.doi.org/10.3233/JAD-170540] [PMID: 29278888]
[http://dx.doi.org/10.1002/ana.26043] [PMID: 33550655]
[http://dx.doi.org/10.1016/j.neuron.2016.04.009] [PMID: 27161522]
[http://dx.doi.org/10.1038/nm0198-097] [PMID: 9427614]
[http://dx.doi.org/10.1016/0306-4522(95)00331-C] [PMID: 8596645]
[http://dx.doi.org/10.1186/s13195-020-00712-4] [PMID: 33148345]
[http://dx.doi.org/10.1016/0304-3940(95)11343-6] [PMID: 7783963]
[http://dx.doi.org/10.1523/JNEUROSCI.22-24-10539.2002] [PMID: 12486146]
[http://dx.doi.org/10.1111/jnc.13417] [PMID: 26526158]
[http://dx.doi.org/10.2174/1567205015666180613111504] [PMID: 29895246]
[http://dx.doi.org/10.1093/brain/awac096] [PMID: 35289363]
[http://dx.doi.org/10.3233/JAD-150262] [PMID: 26401700]
[http://dx.doi.org/10.1093/brain/awy132] [PMID: 29850777]
[http://dx.doi.org/10.1097/WAD.0b013e3181f5dd97] [PMID: 20847636]
[http://dx.doi.org/10.1016/S0028-3908(99)00157-4] [PMID: 10698015]
[PMID: 15038457]
[http://dx.doi.org/10.1002/(SICI)1099-1166(199809)13:9<625::AID-GPS835>3.0.CO;2-2] [PMID: 9777427]
[http://dx.doi.org/10.1016/j.jneumeth.2020.109040] [PMID: 33345945]
[http://dx.doi.org/10.3389/fcomp.2020.551481]
[http://dx.doi.org/10.1038/s41598-020-74399-w] [PMID: 33547343]
[http://dx.doi.org/10.1093/brain/awaa137] [PMID: 32357201]
[http://dx.doi.org/10.1038/s41598-019-54548-6] [PMID: 31796817]
[http://dx.doi.org/10.1016/j.concog.2018.12.003] [PMID: 30593998]
[http://dx.doi.org/10.1002/jnr.23827] [PMID: 27870425]
[http://dx.doi.org/10.1016/j.plipres.2010.09.001] [PMID: 20854843]
[http://dx.doi.org/10.1038/s41467-017-01444-0] [PMID: 29133888]
[http://dx.doi.org/10.1038/s41598-021-97117-6] [PMID: 34475505]
[http://dx.doi.org/10.1177/0271678X20952012] [PMID: 32936729]
[http://dx.doi.org/10.1016/j.neuroimage.2022.118966] [PMID: 35122970]
[http://dx.doi.org/10.1212/01.WNL.0000106462.72282.90] [PMID: 14872024]
[http://dx.doi.org/10.1136/jnnp.71.4.441] [PMID: 11561025]
[http://dx.doi.org/10.1159/000324711] [PMID: 21494034]
[http://dx.doi.org/10.1515/revneuro-2015-0019] [PMID: 26444348]
[http://dx.doi.org/10.1016/j.neurobiolaging.2021.11.004] [PMID: 34963063]
[http://dx.doi.org/10.1016/S1474-4422(07)70106-0] [PMID: 17509484]
[http://dx.doi.org/10.1016/0306-4522(95)00014-A] [PMID: 7477910]
[http://dx.doi.org/10.3389/fnagi.2021.639529] [PMID: 34149392]
[http://dx.doi.org/10.3233/JAD-210140] [PMID: 34151793]
[http://dx.doi.org/10.3389/fphar.2020.00279] [PMID: 32231570]
[http://dx.doi.org/10.1016/j.jalz.2018.04.008] [PMID: 29907423]
[http://dx.doi.org/10.1038/s41582-018-0032-9] [PMID: 29985474]
[http://dx.doi.org/10.1001/jama.1997.03550160069041] [PMID: 9343467]
[http://dx.doi.org/10.1111/ene.13987] [PMID: 31102429]
[http://dx.doi.org/10.3233/JAD-181234] [PMID: 31127771]
[http://dx.doi.org/10.1177/1745506518817995]
[PMID: 28179815]
[http://dx.doi.org/10.1016/j.yfrne.2020.100879] [PMID: 33137359]
[http://dx.doi.org/10.3389/fnagi.2019.00315] [PMID: 31803046]
[http://dx.doi.org/10.1515/revneuro-2017-0066] [PMID: 29466242]
[http://dx.doi.org/10.1093/jnen/nlw047] [PMID: 27297671]
[http://dx.doi.org/10.18632/oncotarget.5185] [PMID: 26397226]
[http://dx.doi.org/10.1001/jama.1993.03500200051032] [PMID: 8487446]
[PMID: 7977338]
[http://dx.doi.org/10.1002/dad2.12121] [PMID: 33251322]
[http://dx.doi.org/10.1212/WNL.0000000000003288] [PMID: 27708128]
[http://dx.doi.org/10.1212/WNL.0000000000002570] [PMID: 26984945]
[http://dx.doi.org/10.3233/JAD-160716] [PMID: 28106548]
[http://dx.doi.org/10.1001/archneur.59.10.1589] [PMID: 12374497]
[http://dx.doi.org/10.3389/frai.2022.680165] [PMID: 35280233]
[http://dx.doi.org/10.34257/GJMRFVOL20IS6PG1] [PMID: 32982106]
[http://dx.doi.org/10.3233/JAD-2006-9S311] [PMID: 16914848]
[http://dx.doi.org/10.1126/science.aad8373]
[http://dx.doi.org/10.1006/exnr.1998.6860] [PMID: 9743577]
[http://dx.doi.org/10.1212/01.WNL.0000098935.36984.25] [PMID: 14694028]
[http://dx.doi.org/10.1016/j.expneurol.2016.04.014] [PMID: 27085394]
[http://dx.doi.org/10.1073/pnas.2121655119] [PMID: 35135885]
[http://dx.doi.org/10.1152/physrev.00042.2020] [PMID: 34254836]
[http://dx.doi.org/10.1126/science.aac8128]
[http://dx.doi.org/10.3389/fnsys.2015.00042] [PMID: 25859189]
[http://dx.doi.org/10.1016/j.brainres.2012.11.020] [PMID: 23178699]
[http://dx.doi.org/10.1016/j.neunet.2011.02.006] [PMID: 21411277]
[http://dx.doi.org/10.3389/fncom.2020.00080] [PMID: 33224031]