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Dysregulation of the brain renin\u2010angiotensin system, particularly hyperactivation of the angiotensin II type\u20101 receptor, contributes to AD pathogenesis. In contrast, activation of the angiotensin II type\u20102 receptor (AT\n                    <jats:sub>2<\/jats:sub>\n                    R) has been linked to neuroprotection and reduced A\u03b2 accumulation. However, the underlying mechanisms of AT\n                    <jats:sub>2<\/jats:sub>\n                    R\u2010related A\u03b2 reduction and the role of AT\n                    <jats:sub>2<\/jats:sub>\n                    R\u2010interacting protein (ATIP), also known as AT\n                    <jats:sub>2<\/jats:sub>\n                    R\u2010binding protein, remain unclear. We aimed to explore the relationship between ATIP and A\u03b2 and tau pathologies as well as brain AT\n                    <jats:sub>2<\/jats:sub>\n                    R protein levels in older adults with AD. Using TOMAHAQ, a method that enables precise examination of numerous peptides across various samples in a single mass spectrometry analysis, we identified a specific human tryptic peptide that enables ATIP quantification. We applied this method to postmortem frontal\u2010cortex samples to measure ATIP levels. Sixty individuals with AD were included, half of whom were users of angiotensin receptor blockers (ARBs). The ATIP peptide was quantifiable in 12 participants. Among these individuals, higher ATIP levels were associated with lower A\u03b2 burden in the frontal\u2010cortex and across multiple brain regions. This association remained significant after adjustment for age and ARB use. In contrast, ATIP levels were not significantly associated with AT\n                    <jats:sub>2<\/jats:sub>\n                    R, which was quantified using TOMAHAQ. This suggests that the relationship between ATIP and A\u03b2 burden may not depend on differences in AT\n                    <jats:sub>2<\/jats:sub>\n                    R abundance. Although causality cannot be established, these findings may suggest a potential protective role for ATIP in AD that warrants further investigation.\n                  <\/jats:p>","DOI":"10.1111\/acel.70686","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T13:50:31Z","timestamp":1788097831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Higher Frontal Cortex Angiotensin Type 2 Receptor\u2010Interacting Protein (\n                    <scp>ATIP<\/scp>\n                    ) Levels Are Associated With a Lower Amyloid\u2010Beta Burden in Postmortem Brains of Older Adults With Alzheimer's Disease"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7560-1287","authenticated-orcid":false,"given":"Caglar","family":"Cosarderelioglu","sequence":"first","affiliation":[{"name":"Division of Geriatric Medicine and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6627-3771","authenticated-orcid":false,"given":"Simion","family":"Kreimer","sequence":"additional","affiliation":[{"name":"The Mass Spectrometry and Proteomics Facility The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma I.","family":"Plaza\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Krieger School of Arts and Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0840-155X","authenticated-orcid":false,"given":"Pablo A.","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Whiting School of Engineering Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-2425","authenticated-orcid":false,"suffix":"Jr.","given":"C. Conover","family":"Talbot","sequence":"additional","affiliation":[{"name":"Institute for Basic Biomedical Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8121-9052","authenticated-orcid":false,"given":"Helmy M.","family":"Siragy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-4758","authenticated-orcid":false,"given":"Ceereena","family":"Ubaida\u2010Mohien","sequence":"additional","affiliation":[{"name":"National Institute on Aging, National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2699-7051","authenticated-orcid":false,"given":"Francine","family":"Grodstein","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"National Institute on Aging, National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-554X","authenticated-orcid":false,"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Walston","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8186-0066","authenticated-orcid":false,"given":"Peter","family":"Abadir","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115978"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000228997.88162.a8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70235"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2019.12.003"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010179939x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000096129"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110036"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.05.019"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00308809"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003\u20100001"},{"issue":"2","key":"e_1_2_12_13_1","first-page":"114","article-title":"The Role of the Renin\u2010Angiotensin System in Amyloid Metabolism of Alzheimer's Disease","volume":"30","author":"Chou C. 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