{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:41:17Z","timestamp":1790847677282,"version":"4.1.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p>Alzheimer's disease (AD) is the most common neurodegenerative disorder caused by neuronal loss that results in cognitive and functional impairment. Formation of neurofibrillary tangles composed of abnormal hyperphosphorylation of tau protein is one of the major pathological hallmarks of AD. Importantly, several neurodegenerative disorders, including AD, are associated with abnormal protein phosphorylation events. However, little is known thus far on global protein phosphorylation changes in AD. We report a phosphoproteomics study examining the frontal gyrus of people with AD and age-matched cognitively normal subjects, using tandem mass tag (TMT) multiplexing technology along with immobilized metal affinity chromatography to enrich phosphopeptides. We identified 4631 phosphopeptides corresponding to 1821 proteins with liquid chromatography-mass spectrometry (MS)\/MS analysis on an Orbitrap Fusion Lumos Tribrid mass spectrometer. Of these, 504 phosphopeptides corresponding to 350 proteins were significantly altered in the AD brain: 389 phosphopeptides increased whereas 115 phosphopeptides decreased phosphorylation. We observed significant changes in phosphorylation of known as well as novel molecules. Using targeted parallel reaction monitoring experiments, we validated the phosphorylation of microtubule-associated protein tau and myristoylated alanine-rich protein kinase C substrate (MARCKS) in control and AD (Control\u2009=\u20096, AD\u2009=\u200911) brain samples. In conclusion, our study provides new evidence on alteration of RNA processing and splicing, neurogenesis and neuronal development, and metabotropic glutamate receptor 5 (GRM5) calcium signaling pathways in the AD brain, and it thus offers new insights to accelerate diagnostics and therapeutics innovation in AD.<\/jats:p>","DOI":"10.1089\/omi.2019.0191","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T14:26:37Z","timestamp":1584455197000},"page":"216-227","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["Multiplexed Phosphoproteomic Study of Brain in Patients with Alzheimer's Disease and Age-Matched Cognitively Healthy Controls"],"prefix":"10.1177","volume":"24","author":[{"given":"Gajanan","family":"Sathe","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India."},{"name":"Institute of Bioinformatics, Bangalore, India."},{"name":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland."},{"name":"Manipal Academy of Higher Education (MAHE), Manipal, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran Kumar","family":"Mangalaparthi","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Jain","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Darrow","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Troncoso","sequence":"additional","affiliation":[{"name":"Department of Pathology and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay","family":"Moghekar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India."},{"name":"Institute of Bioinformatics, Bangalore, India."},{"name":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland."},{"name":"Manipal Academy of Higher Education (MAHE), Manipal, India."},{"name":"Department of Biological Chemistry, Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.19718"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121119298"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.110957"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2017.3036"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310249110"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2018.04.027"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.4161\/pri.21767"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1240"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/329098"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.794602"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62962-8"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04829.x"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400189"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1842"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075025"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065004"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2017.038"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24980"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.8014"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2009.10.010"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/356618a0"},{"key":"e_1_3_4_23_1","first-page":"34309","article-title":"Proteomic analysis of human Nop56p-associated pre-ribosomal ribonucleoprotein complexes","volume":"278","author":"Hayano T","year":"2003","unstructured":"Hayano T, , Yanagida M, , Yamauchi Y, et al. (2003). Proteomic analysis of human Nop56p-associated pre-ribosomal ribonucleoprotein complexes. Possible link between Nop56p and the nucleolar protein treacle responsible for Treacher Collins syndrome. J Biol Chem, 278, 34309\u201334319.","journal-title":"Possible link between Nop56p and the nucleolar protein treacle responsible for Treacher Collins syndrome. J Biol Chem"},{"key":"e_1_3_4_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq200"},{"key":"e_1_3_4_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403678101"},{"key":"e_1_3_4_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200003200-00042"},{"key":"e_1_3_4_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91476-U"},{"key":"e_1_3_4_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2834"},{"key":"e_1_3_4_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9836"},{"key":"e_1_3_4_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2757-14.2015"},{"key":"e_1_3_4_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-017-1732-x"},{"key":"e_1_3_4_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/gtc.12399"},{"key":"e_1_3_4_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075762"},{"key":"e_1_3_4_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8794-6"},{"key":"e_1_3_4_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01150-x"},{"key":"e_1_3_4_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.36"},{"key":"e_1_3_4_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2017.1384697"},{"key":"e_1_3_4_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-232-2_6"},{"key":"e_1_3_4_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-015-0111-4"},{"key":"e_1_3_4_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.029"},{"key":"e_1_3_4_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2011.01343.x"},{"key":"e_1_3_4_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5410.2083"},{"key":"e_1_3_4_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-018-9205-1"},{"key":"e_1_3_4_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201800105"},{"key":"e_1_3_4_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-016-9114-0"},{"key":"e_1_3_4_46_1","first-page":"693","article-title":"Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues","volume":"64","author":"Shin RW","year":"1991","unstructured":"Shin RW, , Iwaki T, , Kitamoto T, , and Tateishi J. (1991). Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab Invest, 64, 693\u2013702.","journal-title":"Lab Invest"},{"key":"e_1_3_4_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.12.4274"},{"key":"e_1_3_4_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"e_1_3_4_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crvi.2006.04.001"},{"key":"e_1_3_4_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1106-1354"},{"key":"e_1_3_4_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.12.4101-4112.2002"},{"key":"e_1_3_4_52_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150417"},{"key":"e_1_3_4_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"e_1_3_4_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(94)90081-7"},{"key":"e_1_3_4_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.06.091"},{"key":"e_1_3_4_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.11.020"},{"key":"e_1_3_4_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.06.011"},{"key":"e_1_3_4_58_1","doi-asserted-by":"publisher","DOI":"10.1159\/000348406"},{"key":"e_1_3_4_59_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720507779939869"},{"key":"e_1_3_4_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07737.x"},{"key":"e_1_3_4_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2324-7"},{"key":"e_1_3_4_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M112.017764"}],"container-title":["OMICS: A Journal of Integrative Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/omi.2019.0191","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/omi.2019.0191","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/omi.2019.0191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T23:03:37Z","timestamp":1777676617000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/omi.2019.0191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":61,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4,1]]}},"alternative-id":["10.1089\/omi.2019.0191"],"URL":"https:\/\/doi.org\/10.1089\/omi.2019.0191","relation":{},"ISSN":["1536-2310","1557-8100"],"issn-type":[{"value":"1536-2310","type":"print"},{"value":"1557-8100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]}}}