{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:22:28Z","timestamp":1791231748137,"version":"4.1.0"},"reference-count":86,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,9,9]],"date-time":"2013-09-09T00:00:00Z","timestamp":1378684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>Failure of elimination of proteins from the brain is a major feature in many neurodegenerative diseases. Insoluble proteins accumulate in brain parenchyma and in walls of cerebral capillaries and arteries. Cerebral amyloid angiopathy (<jats:styled-content style=\"fixed-case\">CAA<\/jats:styled-content>) is a descriptive term for amyloid in vessel walls. Here, we adopt the term protein elimination failure angiopathy (<jats:styled-content style=\"fixed-case\">PEFA<\/jats:styled-content>) to focus on mechanisms involved in the pathogenesis of a spectrum of disorders that exhibit both unique and common features of protein accumulation in blood vessel walls. We review (a) normal pathways and mechanisms by which proteins and other soluble metabolites are eliminated from the brain along 100\u2010 to 150\u2010nm\u2010thick basement membranes in walls of cerebral capillaries and arteries that serve as routes for lymphatic drainage of the brain; (b) a spectrum of proteins involved in <jats:styled-content style=\"fixed-case\">PEFA<\/jats:styled-content>; and (c) changes that occur in artery walls and contribute to failure of protein elimination. We use accumulation of amyloid beta (<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2), prion protein and granular osmiophilic material (<jats:styled-content style=\"fixed-case\">GOM<\/jats:styled-content>) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (<jats:styled-content style=\"fixed-case\">CADASIL<\/jats:styled-content>) as examples of different factors involved in the aetiology and pathogenesis of <jats:styled-content style=\"fixed-case\">PEFA<\/jats:styled-content>. Finally, we discuss how knowledge of factors involved in <jats:styled-content style=\"fixed-case\">PEFA<\/jats:styled-content> may help to focus on new therapies for neurodegenerative diseases. When <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2 (following immunotherapy) and prion protein are released from brain parenchyma they deposit in walls of cerebral capillaries and arteries; <jats:styled-content style=\"fixed-case\">GOM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">CADASIL<\/jats:styled-content> accumulates primarily in artery walls. Therefore, the focus of therapy for protein clearance in neurodegenerative disease should perhaps be on facilitating perivascular elimination of proteins and reducing <jats:styled-content style=\"fixed-case\">PEFA<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/nan.12042","type":"journal-article","created":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T09:20:39Z","timestamp":1363252839000},"page":"593-611","source":"Crossref","is-referenced-by-count":193,"title":["Review: Cerebral amyloid angiopathy, prion angiopathy, <scp>CADASIL<\/scp> and the spectrum of protein elimination failure angiopathies (<scp>PEFA<\/scp>) in neurodegenerative disease with a focus on therapy"],"prefix":"10.1111","volume":"39","author":[{"given":"R. O.","family":"Carare","sequence":"first","affiliation":[{"name":"Clinical Neurosciences and Experimental Sciences Faculty of Medicine University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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