{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:46:44Z","timestamp":1791406004258,"version":"4.3.3"},"reference-count":27,"publisher":"SAGE Publications","issue":"2-3","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rejuvenation Research"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>The local renin\u2013angiotensin system (RAS) in the brain is a multitasking system controlling a plethora of essential functions such as neurogenic hypertension, baroreflexes, and sympathetic activity. Aside from its vasoactive actions, brain angiotensin II (AT-II) has also been implicated in the pathogenesis of cognitive decline, and beneficial effects of angiotensin receptor blockers (ARBs) in Alzheimer (AD) and Parkinson diseases (PD) are suggested. However, the use of ARBs at antihypertensive dosages would lead to unwanted hypotensive reactions in AD patients. Here we treated the APP\/PS1 transgenic mouse model of AD with the ARB losartan (10\u2009mg\/kg body weight) to determine whether blockade of the AT-II receptor subtype 1 (AT1-R) with intranasal losartan, using at a dosage far below its systemic antihypertensive dose, could maintain its neuroprotective effects independent of its systemic vasoactive action. Intranasal losartan treatment (10\u2009mg\/kg every other day for 2 months) of APP\/PS1 mice decreased amyloid \u03b2 (A\u03b2) plaques 3.7-fold. Blood serum levels of interleukin-12 (IL-12)p40\/p70, IL-1\u03b2, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in the vehicle-treated APP\/PS1 mice. Intranasal losartan not only decreased IL-12p40\/p70, IL-1\u03b2, and GM-CSF, but also increased IL-10, which suppresses inflammation. Furthermore, losartan markedly increased tyrosine hydroxylase expression in the striatum and locus coeruleus. In conclusion, losartan exerts direct neuroprotective effects via its A\u03b2-reducing and antiinflammatory effects in the central nervous system (CNS). Therefore, intranasal losartan and potentially other ARBs, at concentrations below their threshold for altering systemic blood pressure, offer a new approach for the treatment of AD.<\/jats:p>","DOI":"10.1089\/rej.2009.0944","type":"journal-article","created":{"date-parts":[[2010,4,7]],"date-time":"2010-04-07T01:33:33Z","timestamp":1270604013000},"page":"195-201","source":"Crossref","is-referenced-by-count":137,"title":["Protective Effects of Intranasal Losartan in the APP\/PS1 Transgenic Mouse Model of Alzheimer Disease"],"prefix":"10.1177","volume":"13","author":[{"given":"Lusine","family":"Danielyan","sequence":"first","affiliation":[{"name":"University Hospital of T\u00fcbingen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Klein","sequence":"additional","affiliation":[{"name":"University Hospital of T\u00fcbingen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah R.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Alzheimer's Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Buadze","sequence":"additional","affiliation":[{"name":"University Hospital of T\u00fcbingen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schwab","sequence":"additional","affiliation":[{"name":"University Hospital of T\u00fcbingen","place":["Germany"]},{"name":"University of T\u00fcbingen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph H.","family":"Gleiter","sequence":"additional","affiliation":[{"name":"University Hospital of T\u00fcbingen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"William H.","family":"Frey","sequence":"additional","affiliation":[{"name":"Alzheimer's Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,4]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0197-4580(00)00259-1","article-title":"Cortical alterations of angiotensin converting enzyme, angiotensin ii and at1 receptor in alzheimer's dementia","volume":"22","author":"Savaskan E","year":"2001","unstructured":"Savaskan E, , Hock C, , Olivieri G, , Bruttel S, , Rosenberg C, , Hulette C, , Muller-Spahn F. Cortical alterations of angiotensin converting enzyme, angiotensin ii and at1 receptor in alzheimer's dementia. Neurobiol Aging, 2001; 22:541\u2013546.","journal-title":"Neurobiol Aging"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90095-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1586\/ern.09.89"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1097\/00005344-200304000-00012","article-title":"Central nervous system 2: Blockade by peripheral administration of at1 receptor blockers","volume":"41","author":"Wang JM","year":"2003","unstructured":"Wang JM, , Tan J, , Leenen FHH. Central nervous system 2: Blockade by peripheral administration of at1 receptor blockers. J Cardiovasc Pharmacol, 2003; 41:593\u2013599.","journal-title":"J Cardiovasc Pharmacol"},{"issue":"3","key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1038\/sj.jhh.1001443","article-title":"Potential for antihypertensive treatment with an at(1)-receptor blocker to reduce dementia in the elderly","volume":"16","author":"Trenkwalder P","year":"2002","unstructured":"Trenkwalder P. Potential for antihypertensive treatment with an at(1)-receptor blocker to reduce dementia in the elderly. J Hum Hypertens, 2002; 16,Suppl 3:S71.","journal-title":"J Hum Hypertens"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1076-7460.2007.07109.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902510209"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.05.029"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-9-S3-S5"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.02.018"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2009.02.001"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1291\/hypres.30.93","article-title":"Arterial blood pressure and renal sodium excretion in dopamine d3 receptor knockout mice","volume":"30","author":"Staudacher T","year":"2007","unstructured":"Staudacher T, , Pech B, , Tappe M, , Gross G, , Muhlbauer B, , Luippold G. Arterial blood pressure and renal sodium excretion in dopamine d3 receptor knockout mice. Hypertens Res, 2007; 30:93\u2013101.","journal-title":"Hypertens Res"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9337-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00671.2004"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.149807"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-2-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/j.1471-4159.2009.05999.x","article-title":"The in- flammatory response in the mptp model of parkinson's disease is mediated by brain angiotensin: Relevance to progression of the disease","volume":"109","author":"Joglar B","year":"2009","unstructured":"Joglar B, , Rodriguez-Pallares J, , Rodriguez-Perez AI, , Rey P, , Guerra MJ, , Labandeira-Garcia JL. The in- flammatory response in the mptp model of parkinson's disease is mediated by brain angiotensin: Relevance to progression of the disease. J Neurochem, 2009; 109:656\u2013669.","journal-title":"J Neurochem"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903958106"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-0925"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31547"},{"key":"e_1_3_3_22_2","doi-asserted-by":"crossref","first-page":"8628","DOI":"10.1523\/JNEUROSCI.1549-07.2007","article-title":"Angiotensin-converting enzyme converts amyloid beta-protein 1\u201342 (abeta[1\u201342] to abeta[1\u201340]), and its inhibition enhances brain abeta deposition","volume":"27","author":"Zou K","year":"2007","unstructured":"Zou K, , Yamaguchi H, , Akatsu H, , Sakamoto T, , Ko M, , Mizoguchi K, , Gong JS, , Yu W, , Yamamoto T, , Kosaka K, , Yanagisawa K, , Michikawa M. 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J Chem Neuroanat, 2007; 34:102\u2013107.","journal-title":"J Chem Neuroanat"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-4-8"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/sj.mp.4001149","article-title":"Combined action of the ace d- and the g-protein beta3 t-allele in major depression: A possible link to cardiovascular disease?","volume":"7","author":"Bondy B","year":"2002","unstructured":"Bondy B, , Baghai TC, , Zill P, , Bottlender R, , Jaeger M, , Minov C, , Schule C, , Zwanzger P, , Rupprecht R, , Engel RR. Combined action of the ace d- and the g-protein beta3 t-allele in major depression: A possible link to cardiovascular disease? 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