{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:20:15Z","timestamp":1791048015110,"version":"4.1.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            We examined the associations among the vascular \u03b2-amyloid levels, smooth muscle actin, wall thickness, and lumen diameter to achieve greater understanding of the arteriolar changes that accompany Alzheimer disease (AD).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            Post-mortem pathology brain specimens from 76 patients with AD and 19 non-AD age control subjects were studied. We analyzed arterioles of the frontal cortex (Brodmann area 10) by immunohistochemistry and morphometry, and derived measures of vascular \u03b2-amyloid level, smooth muscle actin (SMA) volume, and arteriolar wall thickness and lumen diameter.\n            <jats:italic>APOE<\/jats:italic>\n            genotype was determined for each case.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Overall, there was a striking reciprocal relationship between arteriolar \u03b2-amyloid volume and smooth muscle actin (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001). In addition, there was a strong positive association between progressively accumulating vascular \u03b2-amyloid and augmentations in both wall thickness (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001) and lumen width (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001). In comparison with non-AD control subjects, smooth muscle actin was decreased in patients clinically diagnosed with AD and was reduced &gt;10-fold in cases with AD pathology (Braak I to VI) compared with those lacking AD neuropathology. Significantly altered composition and structure of cortical vessels in pre-Braak stages corroborated our hypothesis that arterioles are devastated early in the AD pathological process. Smooth muscle actin, arteriolar wall thickness, and luminal diameter did not vary with Braak stage severity (\n            <jats:italic>P<\/jats:italic>\n            &gt;0.05), indicating that substantial arteriolar damage may precede at least some of the interstitial plaques and neuronal tangles. Moreover, the structural and biochemical arteriolar abnormalities did not vary as a function of\n            <jats:italic>APOE<\/jats:italic>\n            genotype (\n            <jats:italic>P<\/jats:italic>\n            &gt;0.05).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            We postulate that in elderly patients, the continually progressing \u03b2-amyloid-associated angiopathy, at the arteriolar level, harms the contractile apparatus and cerebral blood flow autoregulation, thereby making the downstream capillaries vulnerable to damage. Collectively, our observations lend further support to the idea that microvascular damage has a role, perhaps relatively early, in the onset of major AD pathology.\n          <\/jats:p>","DOI":"10.1161\/strokeaha.107.493429","type":"journal-article","created":{"date-parts":[[2008,2,8]],"date-time":"2008-02-08T02:36:24Z","timestamp":1202438184000},"page":"814-821","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["Cerebral Cortical Arteriolar Angiopathy, Vascular Beta-Amyloid, Smooth Muscle Actin, Braak Stage, and\n            <i>APOE<\/i>\n            Genotype"],"prefix":"10.1161","volume":"39","author":[{"given":"Edward G.","family":"Stopa","sequence":"first","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag","family":"Butala","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Salloway","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad E.","family":"Johanson","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemarie","family":"Tavares","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Hovanesian","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Hulette","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Vitek","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.G.S., P.B., R.T., V.H.), Psychiatry and Human Behavior (S.S., R.A.C.), and Clinical Neurosciences (E.G.S., S.S., C.E.J.), Warren Alpert Medical School of Brown University, Providence, RI; the Department of Computer Science and Statistics (L.G.), University of Rhode Island, Kingston, RI; and Departments of Medicine (Neurology Division) and Pathology (Neuropathology Division) (C.M.H., M.P.V.), Bryan Alzheimer Disease Research Center, Duke University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00966.2005"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2005.tb00103.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2004.02.031"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/156720205774322610"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000085069"},{"key":"e_1_3_2_6_2","first-page":"239","volume":"46","year":"2004","unstructured":"Weller RO, Cohen NR, Nicoll JA. 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