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A\u03b2 is thought to be the causative agent for Alzheimer\u2019s disease (AD). Using positron emission tomography imaging, we have shown that BBB P\u2010gp activity is reduced in AD, as quantified by the\n                    <jats:italic>in vivo<\/jats:italic>\n                    brain distribution of the P\u2010gp probe [\n                    <jats:sup>11<\/jats:sup>\n                    C]\u2010verapamil. Therefore, the aim of this study was to determine whether this reduced BBB P\u2010gp activity in AD was due to decreased P\u2010gp abundance at the BBB. Using targeted proteomics, we quantified the abundance of P\u2010gp and other drug transporters in gray matter brain microvessels isolated from 43 subjects with AD and 38 age\u2010matched controls (AMCs) from regions affected by AD (hippocampus and the parietal lobe of the brain cortex) and not affected by AD (cerebellum). First, P\u2010gp abundance was decreased in the BBB of the hippocampus vs. the cerebellum in both subjects with AD and AMCs, and therefore was not AD\u2010related. In addition, gray matter BBB abundance of P\u2010gp (and of other transporters) in the hippocampus and the parietal lobe was not different between AD and AMC. The gray matter BBB abundance of all drug transporters decreased with age, likely due to age\u2010dependent decrease in the density of brain microvessels. Collectively, the observed reduced\n                    <jats:italic>in vivo<\/jats:italic>\n                    cerebral BBB P\u2010gp activity in AD cannot be explained by reduced abundance of P\u2010gp at the BBB. Nevertheless, the drug transporter abundance at the human gray matter BBB data provided here can be used to predict brain distribution of drugs targeted to treat CNS diseases, including AD.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2035","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T21:50:56Z","timestamp":1599169856000},"page":"667-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Abundance of P\u2010Glycoprotein and Other Drug Transporters at the Human Blood\u2010Brain Barrier in Alzheimer\u2019s Disease: A Quantitative Targeted Proteomic Study"],"prefix":"10.1111","volume":"109","author":[{"given":"Flavia","family":"Storelli","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Billington","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya R.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jashvant D.","family":"Unadkat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.01.010"},{"key":"e_1_2_10_2_1","unstructured":"World Health Organization & Alzheimer\u2019s Disease International Dementia: a public health priority<https:\/\/www.who.int\/mental_health\/publications\/dementia_report_2012\/en\/> (2012)."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.56"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1197623"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1438"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4017"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1769-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.12.005"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.07.017"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15148"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25247"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.113.130161"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.08.034"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.05.020"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.09.015"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200210000-00005"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b01189"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052587399"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-018-0254-9"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1373"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2007.08.005"},{"key":"e_1_2_10_25_1","first-page":"37","article-title":"Characterization and immunohistochemical localization of alpha 2\u2010macroglobulin receptor (low\u2010density lipoprotein receptor\u2010related protein) in human brain","volume":"141","author":"Wolf B.B.","year":"1992","journal-title":"Am. 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