{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T10:07:21Z","timestamp":1789812441226,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T00:00:00Z","timestamp":1306368000000},"content-version":"vor","delay-in-days":145,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Alzheimer's Disease"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:p>Alzheimer\u2032s disease (AD), the most common type of dementia among older people, is characterized by the accumulation of<jats:italic>\u03b2<\/jats:italic>\u2010amyloid (A<jats:italic>\u03b2<\/jats:italic>) senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Despite major advances in understanding the molecular etiology of the disease, progress in the clinical treatment of AD patients has been extremely limited. Therefore, new and more effective therapeutic approaches are needed. Accumulating evidence from human and animal studies suggests that the long\u2010term consumption of caffeine, the most commonly used psychoactive drug in the world, may be protective against AD. The mechanisms underlying the suggested beneficial effect of caffeine against AD remain to be elucidated. In recent studies, several potential neuroprotective effects of caffeine have been proposed. Interestingly, a recent study in rats showed that the long\u2010term consumption of caffeine increased cerebrospinal fluid (CSF) production, associated with the increased expression of Na<jats:sup>+<\/jats:sup>\u2010K<jats:sup>+<\/jats:sup>ATPase and increased cerebral blood flow. Compromised function of the choroid plexus and defective CSF production and turnover, with diminished clearance of A<jats:italic>\u03b2<\/jats:italic>, may be one mechanism implicated in the pathogenesis of late\u2010onset AD. If reduced CSF turnover is a risk factor for AD, then therapeutic strategies to improve CSF flow are reasonable. In this paper, we hypothesize that long\u2010term caffeine consumption could exert protective effects against AD at least in part by facilitating CSF production, turnover, and clearance. Further, we propose a preclinical experimental design allowing evaluation of this hypothesis.<\/jats:p>","DOI":"10.4061\/2011\/617420","type":"journal-article","created":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T17:33:47Z","timestamp":1306431227000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine\u2032s Protective Effect against Alzheimer\u2032s Disease"],"prefix":"10.1155","volume":"2011","author":[{"given":"Peter","family":"Wostyn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debby","family":"Van Dam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Audenaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Paul","family":"De Deyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,5,26]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2007.10.011"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2008.148064"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2009.12.004"},{"key":"e_1_2_7_4_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3233\/JAD-2010-1376","article-title":"Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer\u2032s and Parkinson\u2032s diseases","volume":"20","author":"Chen X.","year":"2010","journal-title":"Journal of Alzheimer\u2032s Disease"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.07.021"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468\u20101331.2002.00421.x"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwf074"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(03)00487\u20103"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1212\/WNL.57.10.1763","article-title":"The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer\u2032s type","volume":"57","author":"Silverberg G. 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