{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:24:02Z","timestamp":1791217442687,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,3,14]]},"abstract":"<jats:p>Hyperphosphorylation of microtubule-associated proteins such as tau\n and neurofilament may underlie the cytoskeletal abnormalities and\n neuronal death seen in several neurodegenerative diseases including\n Alzheimer's disease. One potential mechanism of microtubule-associated\n protein hyperphosphorylation is augmented activity of protein kinases\n known to associate with microtubules, such as cdk5 or GSK3\u03b2. Here we\n show that tau and neurofilament are hyperphosphorylated in transgenic\n mice that overexpress human p25, an activator of cdk5. The p25\n transgenic mice display silver-positive neurons using the Bielschowsky\n stain. Disturbances in neuronal cytoskeletal organization are apparent\n at the ultrastructural level. These changes are localized predominantly\n to the amygdala, thalamus\/hypothalamus, and cortex. The p25\n transgenic mice display increased spontaneous locomotor activity and\n differences from control in the elevated plus-maze test. The\n overexpression of an activator of cdk5 in transgenic mice results in\n increased cdk5 activity that is sufficient to produce\n hyperphosphorylation of tau and neurofilament as well as cytoskeletal\n disruptions reminiscent of Alzheimer's disease and other\n neurodegenerative diseases.<\/jats:p>","DOI":"10.1073\/pnas.040577797","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"2910-2915","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":287,"title":["Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5"],"prefix":"10.1073","volume":"97","author":[{"given":"Michael K.","family":"Ahlijanian","sequence":"first","affiliation":[{"name":"Departments of CNS Discovery, Pathology, and\r Genetic Technologies, Pfizer Central Research, Eastern\r Point Road, Groton, CT 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Pathology, and\r Genetic Technologies, Pfizer Central Research, Eastern\r Point Road, Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Departments of CNS Discovery, Pathology, and\r Genetic Technologies, Pfizer Central Research, Eastern\r Point Road, Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Coskran","sequence":"additional","affiliation":[{"name":"Departments of CNS Discovery, Pathology, and\r Genetic Technologies, Pfizer Central Research, Eastern\r Point Road, Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Carlo","sequence":"additional","affiliation":[{"name":"Departments of CNS Discovery, Pathology, and\r Genetic Technologies, Pfizer Central Research, Eastern\r Point Road, Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia 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