{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T18:50:06Z","timestamp":1776106206363,"version":"3.50.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[1998,7,1]],"date-time":"1998-07-01T00:00:00Z","timestamp":899251200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[1998,7]]},"DOI":"10.1038\/nm0798-827","type":"journal-article","created":{"date-parts":[[2004,8,19]],"date-time":"2004-08-19T02:15:09Z","timestamp":1092881709000},"page":"827-831","source":"Crossref","is-referenced-by-count":428,"title":["Aging renders the brain vulnerable to amyloid \u03b2-protein neurotoxicity"],"prefix":"10.1038","volume":"4","author":[{"given":"Changiz","family":"Guela","sequence":"first","affiliation":[]},{"given":"Chuang-Kuo","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Saroff","sequence":"additional","affiliation":[]},{"given":"Alfredo","family":"Lorenzo","sequence":"additional","affiliation":[]},{"given":"Menglan","family":"Yuan","sequence":"additional","affiliation":[]},{"given":"Bruce A.","family":"Yankner","sequence":"additional","affiliation":[]}],"member":"297","reference":[{"key":"BFnm0798827_CR1","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/S0006-291X(84)80190-4","volume":"120","author":"GG Glenner","year":"1984","unstructured":"Glenner, G.G. & Wong, C.W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120, 885\u2013890 (1984).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnm0798827_CR2","doi-asserted-by":"publisher","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","volume":"82","author":"CL Masters","year":"1985","unstructured":"Masters, C.L. et al. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc. Natl. Acad. Sci. USA 82, 4245\u20134249 (1985).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0798827_CR3","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/S0896-6273(00)80115-4","volume":"16","author":"BA Yankner","year":"1996","unstructured":"Yankner, B.A. Mechanisms of Neuronal Degeneration in Alzheimer's Disease. Neuron 16, 921\u2013932 (1996).","journal-title":"Neuron"},{"key":"BFnm0798827_CR4","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1126\/science.275.5300.630","volume":"275","author":"DJ Selkoe","year":"1997","unstructured":"Selkoe, D.J. Alzheimer's disease: Gentoypes, phenotypes and treatments. Science 275, 630\u2013631 (1997).","journal-title":"Science"},{"key":"BFnm0798827_CR5","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1126\/science.2218531","volume":"250","author":"BA Yankner","year":"1990","unstructured":"Yankner, B.A., Duffy, L.K. & Kirschner, D.A. Neurotrophic and neurotoxic effects of amyloid \u03b2 protein: reversal by tachykinin neuropeptides. Science 250, 279\u2013282 (1990).","journal-title":"Science"},{"key":"BFnm0798827_CR6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/0006-8993(91)91553-D","volume":"563","author":"CJ Pike","year":"1991","unstructured":"Pike, C.J., Walencewicz, A.J., Glabe, C.G. & Cotman, C.W. In vitro aging of \u03b2-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res. 563, 311\u2013314 (1991).","journal-title":"Brain Res."},{"key":"BFnm0798827_CR7","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/0197-4580(92)90065-6","volume":"13","author":"J Busciglio","year":"1992","unstructured":"Busciglio, J., Lorenzo, A. & Yankner, B.A. Methodological variables in the assessment of \u03b2 amyloid neurotoxicity. Neurobiol. Aging 13, 609\u2013612 (1992).","journal-title":"Neurobiol. Aging"},{"key":"BFnm0798827_CR8","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0006-8993(93)90295-X","volume":"621","author":"MP Mattson","year":"1993","unstructured":"Mattson, M.P., Tomaselli, K.J. & Rydel, R.E. Calcium-destabilizing and neurodegenerative effects of aggregated beta-amyloid peptide are attenuated by basic FGF. Brain Res. 621, 35\u201349 (1993).","journal-title":"Brain Res."},{"key":"BFnm0798827_CR9","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1523\/JNEUROSCI.13-04-01676.1993","volume":"13","author":"CJ Pike","year":"1993","unstructured":"Pike, C.J., Burdick, D., Walencewicz, A.J., Glabe, C.G. & Cotman, C.W. Neurodegeneration induced by \u03b2-amyloid peptides in vitro: The role of peptide assembly state. J. Neurosci.. 13, 1676\u20131687 (1993).","journal-title":"J. Neurosci."},{"key":"BFnm0798827_CR10","doi-asserted-by":"publisher","first-page":"12243","DOI":"10.1073\/pnas.91.25.12243","volume":"91","author":"A Lorenzo","year":"1994","unstructured":"Lorenzo, A. & Yankner, B.A. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc. Natl. Acad. Sci. USA 91, 12243\u201312247 (1994).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0798827_CR11","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1006\/neur.1995.0003","volume":"4","author":"DR Howlett","year":"1995","unstructured":"Howlett, D.R. et al. Aggregation state and neurotoxic properties of Alzheimer beta-amyloid peptide. Neurodegen. 4, 23\u201332 (1995).","journal-title":"Neurodegen."},{"key":"BFnm0798827_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/352239a0","volume":"352","author":"D Quon","year":"1991","unstructured":"Quon, D. et al. Formation of \u03b2-amyloid protein deposits in brains of transgenic mice. Nature 352, 239\u2013241 (1991).","journal-title":"Nature"},{"key":"BFnm0798827_CR13","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/373523a0","volume":"373","author":"D Games","year":"1995","unstructured":"Games, D. et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F \u03b2-amyloid precursor protein. Nature 373, 523\u2013527 (1995).","journal-title":"Nature"},{"key":"BFnm0798827_CR14","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1126\/science.274.5284.99","volume":"274","author":"K Hsiao","year":"1996","unstructured":"Hsiao, K. et al. Correlative memory deficits, Abeta elevation and amyloid plaques in transgenic mice. Science 274, 99\u2013102 (1996).","journal-title":"Science"},{"key":"BFnm0798827_CR15","doi-asserted-by":"publisher","first-page":"13287","DOI":"10.1073\/pnas.94.24.13287","volume":"94","author":"C Sturchler-Pierrat","year":"1997","unstructured":"Sturchler-Pierrat, C. et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl. Acad. Sci. U.S.A. 94, 13287\u201313292 (1997).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"BFnm0798827_CR16","doi-asserted-by":"publisher","first-page":"7053","DOI":"10.1523\/JNEUROSCI.17-18-07053.1997","volume":"17","author":"MC Irizarry","year":"1997","unstructured":"Irizarry, M.C. et al. Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J. Neurosci. 17, 7053\u20137059 (1997).","journal-title":"J. Neurosci."},{"key":"BFnm0798827_CR17","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1111\/j.1471-4159.1986.tb08501.x","volume":"46","author":"DJ Selkoe","year":"1986","unstructured":"Selkoe, D.J., Abraham, C.R., Podlisny, M.B. & Duffy, L.B. Isolation of low molecular wieght proteins from amyloid plaque fibers in Alzheimer's disease. J. Neurochem. 46, 1820\u20131834 (1986).","journal-title":"J. Neurochem."},{"key":"BFnm0798827_CR18","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0006-8993(85)91298-3","volume":"361","author":"RG Struble","year":"1985","unstructured":"Struble, R.G., Price, D.L., Jr., Cork, L.C. & Price, D.L. Senile plaques in cortex of aged normal monkey. Brain Res. 361, 267\u2013275 (1985).","journal-title":"Brain Res."},{"key":"BFnm0798827_CR19","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1126\/science.3544219","volume":"235","author":"DJ Selkoe","year":"1987","unstructured":"Selkoe, D.J., Bell, D.S., Podlisny, M.B., Price, D.L. & Cork, L.C. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science 235, 873\u2013877 (1987).","journal-title":"Science"},{"key":"BFnm0798827_CR20","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/j.1749-6632.1993.tb23054.x","volume":"695","author":"EM Mandelkov","year":"1993","unstructured":"Mandelkov, E.M. et al. Microtubule-associated protein tau, paired helical filaments, and phosphorylation. Ann. NY Acad. Sci. 695, 209\u2013216 (1993).","journal-title":"Ann. NY Acad. Sci."},{"key":"BFnm0798827_CR21","doi-asserted-by":"publisher","first-page":"7247","DOI":"10.1073\/pnas.88.16.7247","volume":"88","author":"NW Kowall","year":"1991","unstructured":"Kowall, N.W., Beal, M.F., Busciglio, J., Duffy, L.K. & Yankner, B.A. An in vivo model for the neurodegenerative effects of \u03b2 amyloid and protection by substance P. Proc. Natl. Acad. Sci. USA 88, 7247\u20137251 (1991).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0798827_CR22","doi-asserted-by":"publisher","first-page":"8362","DOI":"10.1073\/pnas.88.19.8362","volume":"88","author":"SA Frautschy","year":"1991","unstructured":"Frautschy, S.A., Baird, A. & Cole, G.M. Effects of injected Alzheimer \u03b2-amyloid cores in rat brain. Proc. Natl. Acad. Sci. USA 88, 8362\u20138366 (1991).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0798827_CR23","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/0896-6273(95)90232-5","volume":"14","author":"J Busciglio","year":"1995","unstructured":"Busciglio, J., Lorenzo, A., Yeh, J. & Yankner, B.A. Beta-Amyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron 14, 879\u2013888 (1995).","journal-title":"Neuron"},{"key":"BFnm0798827_CR24","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/0197-4580(92)90053-Z","volume":"13","author":"NW Kowall","year":"1992","unstructured":"Kowall, N.W., McKee, A.C., Yankner, B.A. & Beal, M.F. In vivo neurotoxicity of beta-amyloid [\u03b2(1\u201340)] and the \u03b2(25\u201335) fragment. Neurobiol. Aging 13, 537\u2013542 (1992).","journal-title":"Neurobiol. Aging"},{"key":"BFnm0798827_CR25","first-page":"17","volume":"142","author":"MB Podlisny","year":"1993","unstructured":"Podlisny, M.B. et al. Microinjection of synthetic amyloid beta-protein in monkey cerebral cortex fails to produce acute neurotoxicity. Am. J. Path. 142, 17\u201324 (1993).","journal-title":"Am. J. Path."},{"key":"BFnm0798827_CR26","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/0197-4580(92)90064-5","volume":"13","author":"PC May","year":"1992","unstructured":"May, P.C. et al. Beta-Amyloid peptide in vitro toxicity: lot-to-lot variability. Neurobiol. Aging 13, 605\u2013607 (1992).","journal-title":"Neurobiol. Aging"},{"key":"BFnm0798827_CR27","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/BF00307691","volume":"80","author":"LC Walker","year":"1990","unstructured":"Walker, L.C., Masters, C., Beyreuther, K. & Price, D.L. Amyloid in the brains of aged normal monkey. Acta Neuropathol. 80, 381\u2013387 (1990).","journal-title":"Acta Neuropathol."},{"key":"BFnm0798827_CR28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/0197-4580(92)90016-Q","volume":"13","author":"N Bons","year":"1991","unstructured":"Bons, N., Mestre, N. & Petter, A. Senile plaques and neurofibrillary changes in the brain of an aged lemurain primate, microcebus murinus. Neurobiol. Aging 13, 99\u2013105 (1991).","journal-title":"Neurobiol. Aging"},{"key":"BFnm0798827_CR29","first-page":"1358","volume":"145","author":"LJ Martin","year":"1994","unstructured":"Martin, L.J., Pardo, C.A., Cork, L.C. & Price, D.L. Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex. Am. J. Pathol. 145, 1358\u20131381 (1994).","journal-title":"Am. J. Pathol."},{"key":"BFnm0798827_CR30","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nm0498-452","volume":"4","author":"R Crook","year":"1998","unstructured":"Crook, R. et al. A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1. Nature Med. 4, 452\u2013455 (1998).","journal-title":"Nature Med."},{"key":"BFnm0798827_CR31","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/ana.410170310","volume":"17","author":"KE Wisniewski","year":"1985","unstructured":"Wisniewski, K.E., Wisniewski, H.M. & Wen, G.Y. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann. Neurol. 17, 278\u2013282 (1985).","journal-title":"Ann. Neurol."},{"key":"BFnm0798827_CR32","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/374647a0","volume":"374","author":"L Meda","year":"1995","unstructured":"Meda, L. et al. Activation of microglial cells by \u03b2-amyloid protein and interferon-\u03b2. Nature 374, 647\u2013650 (1995).","journal-title":"Nature"},{"key":"BFnm0798827_CR33","doi-asserted-by":"publisher","first-page":"6021","DOI":"10.1523\/JNEUROSCI.16-19-06021.1996","volume":"16","author":"D Giulian","year":"1996","unstructured":"Giulian, D. et al. Specific domains of \u03b2-amyloid from Alzheimer plague elicit neuron killing in human microglia. J. Neurosci. 16, 6021\u20136037 (1996).","journal-title":"J. Neurosci."},{"key":"BFnm0798827_CR34","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1523\/JNEUROSCI.18-06-02161.1998","volume":"18","author":"DT Weldon","year":"1998","unstructured":"Weldon, D.T. et al. Fibrillar \u03b2amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo J. Neurosci. 18, 2161\u20132173 (1998).","journal-title":"J. Neurosci."},{"key":"BFnm0798827_CR35","first-page":"447","volume-title":"Alzheimer's Disease: Biology, Diagnosis and Therapeutics","author":"P Frey","year":"1997","unstructured":"Frey, P., Sunderji, S. & Waridel, C. in Alzheimer's Disease: Biology, Diagnosis and Therapeutics (eds. Iqbal, K., Winblad, B., Nishimura, T., Takeda, M. & Wisniewski, H.M.) 447\u2013453 (Wiley and Sons, Chichester, 1997)."},{"key":"BFnm0798827_CR36","doi-asserted-by":"publisher","first-page":"5827","DOI":"10.1073\/pnas.87.15.5827","volume":"87","author":"SG Greenberg","year":"1990","unstructured":"Greenberg, S.G. & Davies, P. A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. Proc. Natl. Acad. Sci. U.S.A. 87, 5827\u20135831 (1990).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm0798-827","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0798-827.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0798-827.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T23:26:49Z","timestamp":1684452409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm0798-827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,7]]},"references-count":36,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1998,7]]}},"alternative-id":["BFnm0798827"],"URL":"https:\/\/doi.org\/10.1038\/nm0798-827","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,7]]}}}