{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:58:43Z","timestamp":1776754723531,"version":"3.51.2"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T00:00:00Z","timestamp":1415836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T00:00:00Z","timestamp":1415836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reductions in hippocampal neurite complexity and synaptic plasticity are believed to contribute to the progressive impairment in episodic memory and the mild cognitive decline that occur particularly in the early stages of Alzheimer\u2019s disease (AD). Despite the functional and therapeutic importance for patients with AD, intervention to rescue or normalize dendritic elaboration and synaptic plasticity is scarcely provided. Here we show that overexpression of <jats:italic>neuritin<\/jats:italic>, an activity-dependent protein, promoted neurite outgrowth and maturation of synapses in parallel with enhanced basal synaptic transmission in cultured hippocampal neurons. Importantly, exogenous application of recombinant neuritin fully restored dendritic complexity as well as spine density in hippocampal neurons prepared from Tg2576 mice, whereas it did not affect neurite branching of neurons from their wild-type littermates. We also showed that soluble recombinant neuritin, when chronically infused into the brains of Tg2576 mice, normalized synaptic plasticity in acute hippocampal slices, leading to intact long-term potentiation. By revealing the protective actions of soluble neuritin against AD-related neural defects, we provide a potential therapeutic approach for patients with AD.<\/jats:p>","DOI":"10.1038\/cddis.2014.478","type":"journal-article","created":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T16:42:38Z","timestamp":1415896958000},"page":"e1523-e1523","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Neuritin can normalize neural deficits of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"5","author":[{"given":"K","family":"An","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J H","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Y","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H G","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S Y","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-151X","authenticated-orcid":false,"given":"H J","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S-J","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T-Y","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Son","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H-S","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J-H","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,11,13]]},"reference":[{"key":"BFcddis2014478_CR1","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1146\/annurev-neuro-060909-153204","volume":"33","author":"Y-C Lin","year":"2010","unstructured":"Lin Y-C, Koleske AJ . Mechanisms of synapse and dendrite maintenance and their disruption in psychiatric and neurodegenerative disorders. Annu Rev Neurosci 2010; 33: 349\u2013378.","journal-title":"Annu Rev Neurosci"},{"key":"BFcddis2014478_CR2","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/S0166-2236(03)00162-0","volume":"26","author":"H Kasai","year":"2003","unstructured":"Kasai H, Matsuzaki M, Noguchi J, Yasumatsu N, Nakahara H . Structure-stability-function relationships of dendritic spines. Trends Neurosci 2003; 26: 360\u2013368.","journal-title":"Trends Neurosci"},{"key":"BFcddis2014478_CR3","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/35104061","volume":"2","author":"H Hering","year":"2001","unstructured":"Hering H, Sheng M . Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci 2001; 2: 880\u2013888.","journal-title":"Nat Rev Neurosci"},{"key":"BFcddis2014478_CR4","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1146\/annurev.neuro.24.1.1071","volume":"24","author":"R Yuste","year":"2001","unstructured":"Yuste R, Bonhoeffer T . Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 2001; 24: 1071\u20131089.","journal-title":"Annu Rev Neurosci"},{"key":"BFcddis2014478_CR5","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1146\/annurev.physiol.64.081501.160008","volume":"64","author":"Ea Nimchinsky","year":"2002","unstructured":"Nimchinsky Ea, Sabatini BL, Svoboda K . Structure and function of dendritic spines. Annu Rev Physiol 2002; 64: 313\u2013353.","journal-title":"Annu Rev Physiol"},{"key":"BFcddis2014478_CR6","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/nature02621","volume":"430","author":"MP Mattson","year":"2004","unstructured":"Mattson MP . Pathways towards and away from Alzheimer\u2019s disease. Nature 2004; 430: 631\u2013639.","journal-title":"Nature"},{"key":"BFcddis2014478_CR7","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1126\/science.1074069","volume":"298","author":"DJ Selkoe","year":"2002","unstructured":"Selkoe DJ . Alzheimer\u2019s disease is a synaptic failure. Science 2002; 298: 789\u2013791.","journal-title":"Science"},{"key":"BFcddis2014478_CR8","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1038\/nprot.2006.356","volume":"1","author":"S Kaech","year":"2006","unstructured":"Kaech S, Banker G . Culturing hippocampal neurons. Nat Protoc 2006; 1: 2406\u20132415.","journal-title":"Nat Protoc"},{"key":"BFcddis2014478_CR9","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nn.3028","volume":"15","author":"I Benilova","year":"2012","unstructured":"Benilova I, Karran E, De Strooper B . The toxic A\u03b2 oligomer and Alzheimer\u2019s disease: an emperor in need of clothes. Nat Neurosci 2012; 15: 349\u2013357.","journal-title":"Nat Neurosci"},{"key":"BFcddis2014478_CR10","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.neuron.2010.11.030","volume":"68","author":"BR Hoover","year":"2010","unstructured":"Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK et al. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 2010; 68: 1067\u20131081.","journal-title":"Neuron"},{"key":"BFcddis2014478_CR11","doi-asserted-by":"publisher","first-page":"38","DOI":"10.2174\/156720508783884620","volume":"5","author":"O Schulte-Herbruggen","year":"2008","unstructured":"Schulte-Herbruggen O, Jockers-Scherubl MC, Hellweg R . Neurotrophins: from pathophysiology to treatment in Alzheimer\u2019s disease. Curr Alzheimer Res 2008; 5: 38\u201344.","journal-title":"Curr Alzheimer Res"},{"key":"BFcddis2014478_CR12","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nrd3366","volume":"10","author":"AH Nagahara","year":"2011","unstructured":"Nagahara AH, Tuszynski MH . Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 2011; 10: 209\u2013219.","journal-title":"Nat Rev Drug Discov"},{"key":"BFcddis2014478_CR13","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nm.1912","volume":"15","author":"AH Nagahara","year":"2009","unstructured":"Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer\u2019s disease. Nat Med 2009; 15: 331\u2013337.","journal-title":"Nat Med"},{"key":"BFcddis2014478_CR14","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1006\/bbrc.1999.1561","volume":"264","author":"SJ Allen","year":"1999","unstructured":"Allen SJ, Wilcock GK, Dawbarn D . Profound and selective loss of catalytic TrkB immunoreactivity in Alzheimer\u2019s disease. Biochem Biophys Res Commun 1999; 264: 648\u2013651.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFcddis2014478_CR15","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1097\/00005072-199907000-00007","volume":"58","author":"I Ferrer","year":"1999","unstructured":"Ferrer I, Mar\u00edn C, Rey MJ, Ribalta T, Goutan E, Blanco R et al. BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J Neuropathol Exp Neurol 1999; 58: 729\u2013739.","journal-title":"J Neuropathol Exp Neurol"},{"key":"BFcddis2014478_CR16","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1073\/pnas.94.6.2648","volume":"94","author":"GS Naeve","year":"1997","unstructured":"Naeve GS, Ramakrishnan M, Kramer R, Hevroni D, Citri Y, Theill LE . Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis. Proc Natl Acad Sci USA 1997; 94: 2648\u20132653.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2014478_CR17","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/363718a0","volume":"363","author":"E Nedivi","year":"1993","unstructured":"Nedivi E, Hevroni D, Naot D, Israeli D, Citri Y . Numerous candidate plasticity-related genes revealed by differential cDNA cloning. Nature 1993; 363: 718\u2013722.","journal-title":"Nature"},{"key":"BFcddis2014478_CR18","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1073\/pnas.93.5.2048","volume":"93","author":"E Nedivi","year":"1996","unstructured":"Nedivi E, Fieldust S, Theill LE, Hevron D . A set of genes expressed in response to light in the adult cerebral cortex and regulated during development. Proc Natl Acad Sci USA 1996; 93: 2048\u20132053.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2014478_CR19","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1523\/JNEUROSCI.22-05-01807.2002","volume":"22","author":"W-CA Lee","year":"2002","unstructured":"Lee W-CA, Nedivi E . Extended plasticity of visual cortex in dark-reared animals may result from prolonged expression of cpg15-like genes. J Neurosci 2002; 22: 1807\u20131815.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR20","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1002\/cne.21649","volume":"507","author":"T Fujino","year":"2008","unstructured":"Fujino T, Wu Z, Lin WC, Phillips MA, Nedivi E . cpg15 and cpg15-2 constitute a family of activity-regulated ligands expressed differentially in the nervous system to promote neurite growth and neuronal survival. J Comp Neurol 2008; 507: 1831\u20131845.","journal-title":"J Comp Neurol"},{"key":"BFcddis2014478_CR21","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1038\/nm1669","volume":"13","author":"JG Hunsberger","year":"2007","unstructured":"Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR et al. Antidepressant actions of the exercise-regulated gene VGF. Nat Med 2007; 13: 1476\u20131482.","journal-title":"Nat Med"},{"key":"BFcddis2014478_CR22","doi-asserted-by":"publisher","first-page":"7999","DOI":"10.1523\/JNEUROSCI.19-18-07999.1999","volume":"19","author":"RA Corriveau","year":"1999","unstructured":"Corriveau RA, Shatz CJ, Nedivi E . Dynamic regulation of cpg15 during activity-dependent synaptic development in the mammalian visual system. J Neurosci 1999; 19: 7999\u20138008.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR23","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1002\/ajmg.b.30996","volume":"153B","author":"D Chandler","year":"2010","unstructured":"Chandler D, Dragovi\u0107 M, Cooper M, Badcock JC, Mullin BH, Faulkner D et al. Impact of Neuritin 1 (NRN1) polymorphisms on fluid intelligence in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 428\u2013437.","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"BFcddis2014478_CR24","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1126\/science.281.5384.1863","volume":"281","author":"E Nedivi","year":"1998","unstructured":"Nedivi E, Wu GY, Cline HT . Promotion of dendritic growth by CPG15, an activity-induced signaling molecule. Science 1998; 281: 1863\u20131866.","journal-title":"Science"},{"key":"BFcddis2014478_CR25","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/79823","volume":"3","author":"I Cantallops","year":"2000","unstructured":"Cantallops I, Haas K, Cline HT . Postsynaptic CPG15 promotes synaptic maturation and presynaptic axon arbor elaboration in vivo. Nat Neurosci 2000; 3: 1004\u20131011.","journal-title":"Nat Neurosci"},{"key":"BFcddis2014478_CR26","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/nn1407","volume":"8","author":"U Putz","year":"2005","unstructured":"Putz U, Harwell C, Nedivi E . Soluble CPG15 expressed during early development rescues cortical progenitors from apoptosis. Nat Neurosci 2005; 8: 322\u2013331.","journal-title":"Nat Neurosci"},{"key":"BFcddis2014478_CR27","doi-asserted-by":"publisher","first-page":"15388","DOI":"10.1523\/JNEUROSCI.0293-12.2012","volume":"32","author":"H Sato","year":"2012","unstructured":"Sato H, Fukutani Y, Yamamoto Y, Tatara E, Takemoto M, Shimamura K et al. Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons. J Neurosci 2012; 32: 15388\u201315402.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR28","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.neuron.2004.12.051","volume":"45","author":"A Javaherian","year":"2005","unstructured":"Javaherian A, Cline HT . Coordinated motor neuron axon growth and neuromuscular synaptogenesis are promoted by CPG15 in vivo. Neuron 2005; 45: 505\u2013512.","journal-title":"Neuron"},{"key":"BFcddis2014478_CR29","doi-asserted-by":"publisher","first-page":"3517","DOI":"10.1523\/JNEUROSCI.2955-13.2014","volume":"34","author":"N Picard","year":"2014","unstructured":"Picard N, Leslie JH, Trowbridge SK, Subramanian J, Nedivi E, Fagiolini M . Aberrant development and plasticity of excitatory visual cortical networks in the absence of cpg15. J Neurosci 2014; 34: 3517\u20133522.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR30","doi-asserted-by":"publisher","first-page":"11378","DOI":"10.1073\/pnas.1201191109","volume":"109","author":"H Son","year":"2012","unstructured":"Son H, Banasr M, Choi M, Chae SY, Licznerski P, Lee B et al. Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress. Proc Natl Acad Sci USA 2012; 109: 11378\u201311383.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2014478_CR31","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1101\/gad.176172.111","volume":"25","author":"T Fujino","year":"2011","unstructured":"Fujino T, Leslie JH, Eavri R, Chen JL, Lin WC, Flanders GH et al. CPG15 regulates synapse stability in the developing and adult brain. Genes Dev 2011; 25: 2674\u20132685.","journal-title":"Genes Dev"},{"key":"BFcddis2014478_CR32","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nrn918","volume":"3","author":"JS Da Silva","year":"2002","unstructured":"Da Silva JS, Dotti CG . Breaking the neuronal sphere: regulation of the actin cytoskeleton in neuritogenesis. Nat Rev Neurosci 2002; 3: 694\u2013704.","journal-title":"Nat Rev Neurosci"},{"key":"BFcddis2014478_CR33","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/cne.902120210","volume":"212","author":"JM Juraska","year":"1982","unstructured":"Juraska JM . The development of pyramidal neurons after eye opening in the visual cortex of hooded rats: a quantitative study. J Comp Neurol 1982; 212: 208\u2013213.","journal-title":"J Comp Neurol"},{"key":"BFcddis2014478_CR34","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/382363a0","volume":"382","author":"ZF Mainen","year":"1996","unstructured":"Mainen ZF, Sejnowski TJ . Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 1996; 382: 363\u2013366.","journal-title":"Nature"},{"key":"BFcddis2014478_CR35","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1152\/jn.2001.85.2.926","volume":"85","author":"P Vetter","year":"2001","unstructured":"Vetter P, Roth A, H\u00e4usser M . Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol 2001; 85: 926\u2013937.","journal-title":"J Neurophysiol"},{"key":"BFcddis2014478_CR36","first-page":"387","volume":"87","author":"DA Sholl","year":"1953","unstructured":"Sholl DA . Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 1953; 87: 387\u2013406.","journal-title":"J Anat"},{"key":"BFcddis2014478_CR37","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1146\/annurev.neuro.31.060407.125646","volume":"31","author":"JN Bourne","year":"2008","unstructured":"Bourne JN, Harris KM . Balancing structure and function at hippocampal dendritic spines. Annu Rev Neurosci 2008; 31: 47\u201367.","journal-title":"Annu Rev Neurosci"},{"key":"BFcddis2014478_CR38","doi-asserted-by":"publisher","first-page":"3399","DOI":"10.1073\/pnas.0511244103","volume":"103","author":"K-W Lee","year":"2006","unstructured":"Lee K-W, Kim Y, Kim A, Helmin K, Nairn A, Greengard P . Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens. Proc Natl Acad Sci USA 2006; 103: 3399\u20133404.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2014478_CR39","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1038\/nrn2501","volume":"9","author":"GA Kerchner","year":"2008","unstructured":"Kerchner GA, Nicoll RA . Silent synapses and the emergence of a postsynaptic mechanism for LTP. Nat Rev Neurosci 2008; 9: 813\u2013825.","journal-title":"Nat Rev Neurosci"},{"key":"BFcddis2014478_CR40","doi-asserted-by":"publisher","first-page":"5795","DOI":"10.1523\/JNEUROSCI.16-18-05795.1996","volume":"16","author":"E Masliah","year":"1996","unstructured":"Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D . Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F \u03b2-amyloid precursor protein and Alzheimer\u2019s disease. J Neurosci 1996; 16: 5795\u20135811.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR41","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1523\/JNEUROSCI.4456-09.2010","volume":"30","author":"H-Y Wu","year":"2010","unstructured":"Wu H-Y, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan Z et al. Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. J Neurosci 2010; 30: 2636\u20132649.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR42","doi-asserted-by":"publisher","first-page":"41534","DOI":"10.1074\/jbc.M112.390260","volume":"287","author":"J-J Yao","year":"2012","unstructured":"Yao J-J, Gao X-F, Chow C-W, Zhan X-Q, Hu C-L, Mei Y-A . Neuritin activates insulin receptor pathway to up-regulate Kv4.2-mediated transient outward K+ current in rat cerebellar granule neurons. J Biol Chem 2012; 287: 41534\u201341545.","journal-title":"J Biol Chem"},{"key":"BFcddis2014478_CR43","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/nature08536","volume":"461","author":"BR Arenkiel","year":"2009","unstructured":"Arenkiel BR, Ehlers MD . Molecular genetics and imaging technologies for circuit-based neuroanatomy. Nature 2009; 461: 900\u2013907.","journal-title":"Nature"},{"key":"BFcddis2014478_CR44","doi-asserted-by":"publisher","first-page":"e104121","DOI":"10.1371\/journal.pone.0104121","volume":"9","author":"Y Choi","year":"2014","unstructured":"Choi Y, Lee K, Ryu J, Kim HG, Jeong AY, Woo R-S et al. Neuritin attenuates cognitive function impairments in Tg2576 mouse model of Alzheimer\u2019s disease. PLoS ONE 2014; 9: e104121.","journal-title":"PLoS ONE"},{"key":"BFcddis2014478_CR45","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1756-6606-6-47","volume":"6","author":"K An","year":"2013","unstructured":"An K, Klyubin I, Kim Y, Jung JH, Mably AJ, O\u2019Dowd ST et al. Exosomes neutralize synaptic-plasticity-disrupting activity of A\u03b2 assemblies in vivo. Mol Brain 2013; 6: 47.","journal-title":"Mol Brain"},{"key":"BFcddis2014478_CR46","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/nn.2785","volume":"14","author":"J Jo","year":"2011","unstructured":"Jo J, Whitcomb DJ, Olsen KM, Kerrigan TL, Lo S-C, Bru-Mercier G et al. A\u03b2(1\u201342) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3\u03b2. Nat Neurosci 2011; 14: 545\u2013547.","journal-title":"Nat Neurosci"},{"key":"BFcddis2014478_CR47","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s10059-011-0077-8","volume":"32","author":"JH Jung","year":"2011","unstructured":"Jung JH, An K, Kwon O Bin, Kim H-S, Kim J-H . Pathway-specific alteration of synaptic plasticity in Tg2576 mice. Mol Cells 2011; 32: 197\u2013201.","journal-title":"Mol Cells"},{"key":"BFcddis2014478_CR48","doi-asserted-by":"publisher","first-page":"6213","DOI":"10.1523\/JNEUROSCI.0664-05.2005","volume":"25","author":"RE Hartman","year":"2005","unstructured":"Hartman RE, Izumi Y, Bales KR, Paul SM, Wozniak DF, Holtzman DM . Treatment with an amyloid-beta antibody ameliorates plaque load, learning deficits, and hippocampal long-term potentiation in a mouse model of Alzheimer\u2019s disease. J Neurosci 2005; 25: 6213\u20136220.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR49","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1152\/physrev.00014.2003","volume":"84","author":"MA Lynch","year":"2004","unstructured":"Lynch MA . Long-term potentiation and memory. Physiol Rev 2004; 84: 87\u2013136.","journal-title":"Physiol Rev"},{"key":"BFcddis2014478_CR50","doi-asserted-by":"publisher","first-page":"5161","DOI":"10.1073\/pnas.0600948103","volume":"103","author":"JS Jacobsen","year":"2006","unstructured":"Jacobsen JS, Wu C-C, Redwine JM, Comery TA, Arias R, Bowlby M et al. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer\u2019s disease. Proc Natl Acad Sci USA 2006; 103: 5161\u20135166.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2014478_CR51","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1523\/JNEUROSCI.22-05-01858.2002","volume":"22","author":"MA Westerman","year":"2002","unstructured":"Westerman MA, Cooper-Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin LH et al. The relationship between A\u03b2 and memory in the Tg2576 mouse model of Alzheimer\u2019s disease. J Neurosci 2002; 22: 1858\u20131867.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR52","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/nature04533","volume":"440","author":"S Lesn\u00e9","year":"2006","unstructured":"Lesn\u00e9 S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006; 440: 352\u2013357.","journal-title":"Nature"},{"key":"BFcddis2014478_CR53","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1523\/JNEUROSCI.21-02-00372.2001","volume":"21","author":"T Kawarabayashi","year":"2001","unstructured":"Kawarabayashi T, Younkin L . Age-dependent changes in brain, CSF, and plasma amyloid \u00ce2 protein in the Tg2576 transgenic mouse model of Alzheimer\u2019s disease. J Neurosci 2001; 21: 372\u2013381.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR54","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1002\/cne.1044","volume":"435","author":"E Nedivi","year":"2001","unstructured":"Nedivi E, Javaherian A, Cantallops I, Cline HT . Developmental regulation of CPG15 expression in Xenopus. J Comp Neurol 2001; 435: 464\u2013473.","journal-title":"J Comp Neurol"},{"key":"BFcddis2014478_CR55","doi-asserted-by":"publisher","first-page":"3274","DOI":"10.1523\/JNEUROSCI.16-10-03274.1996","volume":"16","author":"JA Gordon","year":"1996","unstructured":"Gordon JA, Stryker MP . Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse. J Neurosci 1996; 16: 3274\u20133286.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR56","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1093\/cercor\/bhj019","volume":"16","author":"S Oray","year":"2006","unstructured":"Oray S, Majewska A, Sur M . Effects of synaptic activity on dendritic spine motility of developing cortical layer v pyramidal neurons. Cereb Cortex 2006; 16: 730\u2013741.","journal-title":"Cereb Cortex"},{"key":"BFcddis2014478_CR57","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nn878","volume":"5","author":"NS Desai","year":"2002","unstructured":"Desai NS, Cudmore RH, Nelson SB, Turrigiano GG . Critical periods for experience-dependent synaptic scaling in visual cortex. Nat Neurosci 2002; 5: 783\u2013789.","journal-title":"Nat Neurosci"},{"key":"BFcddis2014478_CR58","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1038\/nn736","volume":"4","author":"M Matsuzaki","year":"2001","unstructured":"Matsuzaki M, Ellis-Davies GC, Nemoto T, Miyashita Y, Iino M, Kasai H . Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 2001; 4: 1086\u20131092.","journal-title":"Nat Neurosci"},{"key":"BFcddis2014478_CR59","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nrm1309","volume":"5","author":"S Mayor","year":"2004","unstructured":"Mayor S, Riezman H . Sorting GPI-anchored proteins. Nat Rev Mol Cell Biol 2004; 5: 110\u2013120.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcddis2014478_CR60","doi-asserted-by":"publisher","first-page":"20315","DOI":"10.1074\/jbc.M601016200","volume":"281","author":"YH Chong","year":"2006","unstructured":"Chong YH, Shin YJ, Lee EO, Kayed R, Glabe CG, Tenner AJ . ERK1\/2 activation mediates Abeta oligomer-induced neurotoxicity via caspase-3 activation and tau cleavage in rat organotypic hippocampal slice cultures. J Biol Chem 2006; 281: 20315\u201320325.","journal-title":"J Biol Chem"},{"key":"BFcddis2014478_CR61","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nn.2709","volume":"14","author":"M D\u2019Amelio","year":"2011","unstructured":"D\u2019Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S, Ferri A et al. Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer\u2019s disease. Nat Neurosci 2011; 14: 69\u201376.","journal-title":"Nat Neurosci"},{"key":"BFcddis2014478_CR62","doi-asserted-by":"publisher","first-page":"11300","DOI":"10.1523\/JNEUROSCI.2270-05.2005","volume":"25","author":"J Jaworski","year":"2005","unstructured":"Jaworski J, Spangler S, Seeburg DP, Hoogenraad CC, Sheng M . Control of dendritic arborization by the phosphoinositide-3\u2019-kinase-Akt-mammalian target of rapamycin pathway. J Neurosci 2005; 25: 11300\u201311312.","journal-title":"J Neurosci"},{"key":"BFcddis2014478_CR63","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/j.cell.2010.03.053","volume":"141","author":"Z Li","year":"2010","unstructured":"Li Z, Jo J, Jia J-M, Lo S-C, Whitcomb DJ, Jiao S et al. Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell 2010; 141: 859\u2013871.","journal-title":"Cell"},{"key":"BFcddis2014478_CR64","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.tins.2009.11.003","volume":"33","author":"CA Hoeffer","year":"2010","unstructured":"Hoeffer CA, Klann E . mTOR signaling: At the crossroads of plasticity, memory and disease. Trends Neurosci 2010; 33: 67\u201375.","journal-title":"Trends Neurosci"},{"key":"BFcddis2014478_CR65","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0092-8674(04)00115-1","volume":"116","author":"RJ Kelleher","year":"2004","unstructured":"Kelleher RJ, Govindarajan A, Jung H-Y, Kang H, Tonegawa S . Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 2004; 116: 467\u2013479.","journal-title":"Cell"},{"key":"BFcddis2014478_CR66","first-page":"1","volume":"5","author":"T Ma","year":"2010","unstructured":"Ma T, Hoeffer CA, Capetillo-Zarate E, Yu F, Wong H, Lin MT et al. Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer\u2019s disease. PLoS ONE 2010; 5: 1\u201310.","journal-title":"PLoS ONE"},{"key":"BFcddis2014478_CR67","doi-asserted-by":"publisher","first-page":"13107","DOI":"10.1074\/jbc.M110.100420","volume":"285","author":"A Caccamo","year":"2010","unstructured":"Caccamo A, Majumder S, Richardson A, Strong R, Oddo S . Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem 2010; 285: 13107\u201313120.","journal-title":"J Biol Chem"},{"key":"BFcddis2014478_CR68","doi-asserted-by":"publisher","first-page":"e9979","DOI":"10.1371\/journal.pone.0009979","volume":"5","author":"P Spilman","year":"2010","unstructured":"Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer\u2019s disease. PLoS ONE 2010; 5: e9979.","journal-title":"PLoS ONE"},{"key":"BFcddis2014478_CR69","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/nprot.2006.86","volume":"1","author":"M Jiang","year":"2006","unstructured":"Jiang M, Chen G . High Ca2+-phosphate transfection efficiency in low-density neuronal cultures. Nat Protoc 2006; 1: 695\u2013700.","journal-title":"Nat Protoc"},{"key":"BFcddis2014478_CR70","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1126\/science.274.5284.99","volume":"274","author":"K Hsiao","year":"1996","unstructured":"Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996; 274: 99\u2013102.","journal-title":"Science"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis2014478.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2014478","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2014478.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T23:22:21Z","timestamp":1672960941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2014478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,13]]},"references-count":70,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11]]}},"alternative-id":["BFcddis2014478"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2014.478","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,13]]},"assertion":[{"value":"21 May 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2014","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2014","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2014","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}