{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:04:42Z","timestamp":1774497882703,"version":"3.50.1"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>One of the puzzling aspects of sporadic Alzheimer\u2019s disease (AD) is how it commences. Changes in one key brain peptide, amyloid-beta (A\u03b2), accompany disease progression, but whether this comprises a trigger or a consequence of AD is still a topic of debate. It is clear however that the cerebral presence of oligomeric A\u03b2 (1\u201342) is a key factor in early AD-pathogenesis. Furthermore, treatment of rodent brains with oligomeric A\u03b2 (1\u201342) either <jats:italic>in vitro<\/jats:italic> or <jats:italic>in vivo<\/jats:italic>, acutely impairs hippocampal synaptic plasticity, creating a link between A\u03b2-pathology and learning impairments. Here, we show that a once-off inoculation of the brains of healthy adult rats with oligomeric A\u03b2 (1\u201342) exerts debilitating effects on the long-term viability of the hippocampus, one of the primary targets of AD. Changes are progressive: months after treatment, synaptic plasticity, neuronal firing and spatial learning are impaired and expression of plasticity-related proteins are changed, in the absence of amyloid plaques. Early changes relate to activation of microglia, whereas later changes are associated with a reconstruction of astroglial morphology. These data suggest that a disruption of A\u03b2 homeostasis may suffice to trigger an irreversible cascade, underlying progressive loss of hippocampal function, that parallels the early stages of AD.<\/jats:p>","DOI":"10.3389\/fnagi.2024.1397901","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T04:39:18Z","timestamp":1722573558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Intracerebral inoculation of healthy non-transgenic rats with a single aliquot of oligomeric amyloid-\u03b2 (1\u201342) profoundly and progressively alters brain function throughout life"],"prefix":"10.3389","volume":"16","author":[{"given":"Marco","family":"Kramer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thu-Huong","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honghong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olena","family":"Shchyglo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane","family":"B\u00f6ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Neubacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Colitti-Klausnitzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Manahan-Vaughan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1002\/jnr.24075","article-title":"Astrocyte dysfunction in Alzheimer disease","volume":"95","author":"Acosta","year":"2017","journal-title":"J. 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Soc. Trans."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.peptides.2009.12.001","article-title":"Controlled in situ preparation of a beta(1-42) oligomers from the isopeptide \"iso-a beta(1-42)\", physicochemical and biological characterization","volume":"31","author":"Bozso","year":"2010","journal-title":"Peptides"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1038\/nn.3435","article-title":"CD33 Alzheimer\u2019s disease locus: altered monocyte function and amyloid biology","volume":"16","author":"Bradshaw","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/386284a0","article-title":"Homer. A protein that selectively binds metabotropic glutamate receptors","volume":"386","author":"Brakeman","year":"1997","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"552073","DOI":"10.3389\/fnmol.2020.552073","article-title":"The interplay between Beta-amyloid 1\u201342 (A\u03b21\u201342)-induced hippocampal inflammatory response, p-tau, vascular pathology, and their synergistic contributions to neuronal death and behavioral deficits","volume":"13","author":"Calvo-Flores Guzm\u00e1n","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref1022","doi-asserted-by":"publisher","first-page":"976","DOI":"10.3389\/fphar.2019.00976","article-title":"Risk factors for alzheimer\u2019s disease: Focus on stress","volume":"10","author":"Caruso","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1093\/arclin\/acw072","article-title":"Computerized structured cognitive training in patients affected by early-stage Alzheimer's disease is feasible and effective: a randomized controlled study","volume":"31","author":"Cavallo","year":"2016","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1742-2094-11-98","article-title":"Neuroinflammation and M2 microglia: the good, the bad, and the inflamed","volume":"11","author":"Cherry","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1111\/j.1469-7580.2007.00724.x","article-title":"Three-dimensional confocal morphometry \u2013 a new approach for studying dynamic changes in cell morphology in brain slices","volume":"210","author":"Chv\u00e1tal","year":"","journal-title":"J. Anat."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1002\/jnr.21113","article-title":"Three-dimensional confocal morphometry reveals structural changes in astrocyte morphology in situ","volume":"85","author":"Chv\u00e1tal","year":"","journal-title":"J. Neurosci. Res."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nn1372","article-title":"Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function","volume":"8","author":"Cleary","year":"2005","journal-title":"Nat. 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Neurobiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e91203","DOI":"10.1371\/journal.pone.0091203","article-title":"Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo","volume":"9","author":"Davis","year":"2014","journal-title":"PLoS One"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.bbi.2023.03.001","article-title":"Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies. Alzheimer's disease neuroimaging initiative","volume":"110","author":"De Bastiani","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The cellular phase of Alzheimer's disease","volume":"164","author":"De Strooper","year":"2016","journal-title":"Cell"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"16","DOI":"10.2174\/187152709787601867","article-title":"Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease","volume":"8","author":"Deane","year":"2009","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.neuro.2012.12.004","article-title":"Neoechinulin a suppresses amyloid-\u03b2 oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity","volume":"35","author":"Dewapriya","year":"2013","journal-title":"Neurotoxicology"},{"key":"ref1024","doi-asserted-by":"publisher","first-page":"e700","DOI":"10.1212\/WNL.0000000000006919","article-title":"Impaired olfaction is associated with cognitive decline and neurodegeneration in the brain","volume":"92","author":"Dintica","year":"2019","journal-title":"Neurology."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1474-9726.2007.00297.x","article-title":"Alterations in intrinsic neuronal excitability during normal aging","volume":"6","author":"Disterhoft","year":"2007","journal-title":"Aging Cell"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.tins.2019.03.003","article-title":"A unifying hypothesis for Alzheimer's disease: from plaques to neurodegeneration","volume":"42","author":"Edwards","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1038\/3305","article-title":"Neurogenesis in the adult human hippocampus","volume":"4","author":"Eriksson","year":"1998","journal-title":"Nat. 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Alzheimer's and Parkinson's diseases: the prion concept in relation to assembled A\u03b2, tau, and \u03b1-synuclein","volume-title":"Science","author":"Goedert","year":"2015"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1093\/cercor\/bhs105","article-title":"Increased cortical and thalamic excitability in freely moving APPswe\/PS1dE9 mice modeling epileptic activity associated with Alzheimer's disease","volume":"23","author":"Gurevicius","year":"2013","journal-title":"Cereb. Cortex"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1085\/jgp.201812032","article-title":"Structure, function, and allosteric modulation of NMDA receptors","volume":"150","author":"Hansen","year":"2018","journal-title":"J. Gen. Physiol."},{"key":"ref31","first-page":"353","article-title":"The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics","volume-title":"Science","author":"Hardy","year":"2002"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3389\/Ffncel.2018.00258","article-title":"Importance of GPCR-Mediated Microglial Activation in Alzheimer's Disease","volume":"12","author":"Haque","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/hipo.22833","article-title":"Novel exploration of positional or directional spatial cues induces arc mRNA expression in different hippocampal subfields: evidence for parallel information processing and the \u201cwhat\u201d stream","volume":"28","author":"Hoang","year":"2018","journal-title":"Hippocampus"},{"key":"ref1008","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1002\/hipo.23333","article-title":"Hippocampal subfield-specific Homer1a expression is triggered by learning-facilitated long-term potentiation and long-term depression at medial perforant path synapses","volume":"31","author":"Hoang","year":"2021","journal-title":"Hippocampus"},{"key":"ref1009","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s00429-023-02694-z","article-title":"Differentiated somatic gene expression is triggered in the dorsal hippocampus and the anterior retrosplenial cortex by hippocampal synaptic plasticity prompted by spatial content learning","volume":"229","author":"Hoang","year":"2023","journal-title":"Brain Structure and Function"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1002\/gps.4537","article-title":"The importance of sustained attention in early Alzheimer's disease","volume":"32","author":"Huntley","year":"2016","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0169-328X(98)00040-0","article-title":"Microglia-specific localisation of a novel calcium binding protein, Iba1","volume":"57","author":"Ito","year":"1998","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref1017","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer\u2019s disease: an updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nature15369","article-title":"Evidence for human transmission of amyloid-? Pathology and cerebral amyloid angiopathy","volume":"525","author":"Jaunmuktane","year":"2015","journal-title":"Nature"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1038\/npp.2014.164","article-title":"Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer\u2019s disease","volume":"39","author":"Jiang","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nature12481","article-title":"Self-propagation of pathogenic protein aggregates in neurodegenerative diseases","volume":"501","author":"Jucker","year":"2013","journal-title":"Nature"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/s41593-018-0238-6","article-title":"Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases","volume":"21","author":"Jucker","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.3390\/biom11091361","article-title":"Beyond the GFAP-astrocyte protein markers in the brain","volume":"11","author":"Jurga","year":"2021","journal-title":"Biomol. Ther."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3389\/fnbeh.2015.00103","article-title":"Acute intracerebral treatment with amyloid-beta (1-42) alters the profile of neuronal oscillations that accompany LTP induction and results in impaired LTP in freely behaving rats","volume":"9","author":"Kalweit","year":"2015","journal-title":"Front. Behav. Neurosci."},{"key":"ref1026","doi-asserted-by":"publisher","first-page":"3606","DOI":"10.1523\/JNEUROSCI.20-10-03606.2000","article-title":"Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice","volume":"20","author":"Kane","year":"2000","journal-title":"JNeurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/325733a0","article-title":"The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor","volume":"325","author":"Kang","year":"1987","journal-title":"Nature"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/bpa.12734","article-title":"A\u03b2 oligomers trigger and accelerate A\u03b2 seeding","volume":"30","author":"Katzmarski","year":"2020","journal-title":"Brain Pathol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1016\/j.neurobiolaging.2014.04.001","article-title":"Amyloid-\u03b2 alters ongoing neuronal activity and excitability in the frontal cortex","volume":"35","author":"Kellner","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"8192","DOI":"10.1073\/pnas.0402650101","article-title":"Hippocampal long-term depression and long-term potentiation encode different aspects of novelty acquisition","volume":"101","author":"Kemp","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.neubiorev.2020.02.012","article-title":"Behavioural and psychological symptoms of dementia in mouse models of Alzheimer's disease-related pathology","volume":"112","author":"Kosel","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1111\/bpa.12536","article-title":"Protein astrogliopathies in human neurodegenerative diseases and aging","volume":"27","author":"Kovacs","year":"2017","journal-title":"Brain Pathol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1126\/science.6494926","article-title":"Prolonged Ca2+\u2212dependent afterhyperpolarizations in hippocampal neurons of aged rats","volume":"226","author":"Landfield","year":"1984","journal-title":"Science"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/jnc.15007","article-title":"A mechanistic hypothesis for the impairment of synaptic plasticity by soluble ab oligomers from Alzheimer's brain","volume":"154","author":"Li","year":"2020","journal-title":"J. Neurochem."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"15396","DOI":"10.1021\/bi971071m","article-title":"Mutations in the transmembrane domain of APP altering gamma-secretase specificity","volume":"36","author":"Lichtenthaler","year":"1997","journal-title":"Biochemistry"},{"key":"ref1023","doi-asserted-by":"publisher","first-page":"e0174561","DOI":"10.1371\/journal.pone.0174561","article-title":"Alzheimer\u2019s amyloid-\u03b2 A2T variant and its N-terminal peptides inhibit amyloid-\u03b2 fibrillization and rescue the induced cytotoxicity","volume":"12","author":"Lin","year":"2017","journal-title":"PLoS ONE."},{"key":"ref1021","doi-asserted-by":"publisher","first-page":"4919","DOI":"10.2147\/IJN.S240953","article-title":"Multifunctional superparamagnetic iron oxide nanoparticles conjugated with A\u03b2 oligomer-specific scFv antibody and class a scavenger receptor activator show early diagnostic potentials for alzheimer\u2019s disease","volume":"15","author":"Liu","year":"2020","journal-title":"Int J Nanomedicine."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1517\/14728222.2014.988707","article-title":"Targeting microglia for the treatment of Alzheimer\u2019s disease","volume":"19","author":"McGeer","year":"2015","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/374647a0","article-title":"Activation of microglial cells by beta-amyloid protein and interferon-gamma","volume":"374","author":"Meda","year":"1995","journal-title":"Nature"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.1523\/JNEUROSCI.5215-08.2009","article-title":"Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy","volume":"29","author":"Minkeviciene","year":"2009","journal-title":"J. Neurosci."},{"key":"ref1025","doi-asserted-by":"publisher","first-page":"5690","DOI":"10.1038\/s41380-021-01150-w","article-title":"Transmission of cerebral amyloid pathology by peripheral administration of misfolded A\u03b2 aggregates","volume":"26","author":"Morales","year":"2021","journal-title":"Mol Psychiatry."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1007\/s11065-014-9267-4","article-title":"The relevance of beta-amyloid on markers of Alzheimer's disease in clinically normal individuals and factors that influence these associations","volume":"24","author":"Mormino","year":"2014","journal-title":"Neuropsychol. Rev."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.bcp.2014.01.008","article-title":"Microglial dysfunction in brain aging and Alzheimer\u2019s disease","volume":"88","author":"Mosher","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"5606","DOI":"10.1073\/pnas.0408483102","article-title":"Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine","volume":"102","author":"Mothet","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/glia.20967","article-title":"Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer\u2019s disease","volume":"58","author":"Olabarria","year":"2010","journal-title":"Glia"},{"key":"ref1005","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.14670\/HH-25.1017","article-title":"Sudan Black B treatment reduces autofluorescence and improves resolution of in situ hybridization specific fluorescent signals of brain sections","volume":"25","author":"Oliveira","year":"2010","journal-title":"Histol Histopathol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/nn.2583","article-title":"Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks","volume":"13","author":"Palop","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.neuron.2007.07.025","article-title":"Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease","volume":"55","author":"Palop","year":"2007","journal-title":"Neuron"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrn3504","article-title":"NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease","volume":"14","author":"Paoletti","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"559","DOI":"10.2174\/1567205016666190321154618","article-title":"Systemic and CNS inflammation crosstalk: implications for Alzheimer's disease","volume":"16","author":"Paouri","year":"2019","journal-title":"Curr. Alzheimers Res."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1021\/cn2001238","article-title":"Isolated amyloid-\u03b2(1\u201342) Protofibrils, but not isolated fibrils, are robust stimulators of microglia","volume":"3","author":"Paranjape","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"ref1011","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/alz.13450","article-title":"ALFA study. Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer\u2019s disease progression","volume":"20","author":"Pelkmans","year":"2024","journal-title":"Alzheimers Dement"},{"key":"ref1003","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1002\/ana.22313","article-title":"Endogenous Amyloid-\u03b2 is Necessary for Hippocampal Synaptic Plasticity and Memory","volume":"69","author":"Puzzo","year":"2011","journal-title":"Ann Neurol."},{"key":"ref1002","doi-asserted-by":"publisher","first-page":"14537","DOI":"10.1523\/JNEUROSCI.2692-08.2008","article-title":"Picomolar Amyloid-\u03b2 Positively Modulates Synaptic Plasticity and Memory in Hippocampus","volume":"28","author":"Puzzo","year":"2008","journal-title":"JNeurosci"},{"key":"ref1016","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.neuropharm.2018.07.021","article-title":"The NMDA receptor antagonist Radiprodil reverses the synaptotoxic effects of different amyloid-beta (A\u03b2) species on long-term potentiation (LTP)","volume":"15","author":"Rammes","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3389\/fnagi.2016.00160","article-title":"Mechanisms of A\u03b2 Clearance and Degradation by Glial Cells","volume":"8","author":"Ries","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/cdd.2008.172","article-title":"Astroglia in dementia and Alzheimer's disease","volume":"16","author":"Rodr\u00edguez","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"7333","DOI":"10.1038\/s41467-022-34538-5","article-title":"Experimental evidence for temporal uncoupling of brain A\u03b2 deposition and neurodegenerative sequelae","volume":"13","author":"Rother","year":"2022","journal-title":"Nature Comm."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.15252\/embj.201797397","article-title":"APP mouse models for Alzheimer's disease preclinical studies","volume":"36","author":"Sasaguri","year":"2017","journal-title":"EMBO J."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref72","first-page":"531","article-title":"Surface complexity of human neocortical astrocytic cells: changes with development, aging, and dementia","volume":"36","author":"Senitz","year":"1995","journal-title":"J. Hirnforsch."},{"key":"ref1020","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1007\/s12035-019-01858-5","article-title":"Alzheimer\u2019s disease and diabetes:Insulin signaling as the bridge linking two pathologies","volume":"57","author":"Shieh","year":"2020","journal-title":"Mol Neurobiol"},{"key":"ref1018","doi-asserted-by":"publisher","first-page":"7278","DOI":"10.1523\/JNEUROSCI.1879-05.2005","article-title":"Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy","volume":"25","author":"Spires","year":"2005","journal-title":"J Neurosci."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1042\/BST0340877","article-title":"Structure and trafficking of NMDA and GABAA receptors","volume":"34","author":"Stephenson","year":"2006","journal-title":"Biochm. Soc. Trans."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"591735","DOI":"10.3389\/fnagi.2021.591735","article-title":"Absence of Pannexin 1 stabilizes hippocampal excitability after intracerebral treatment with A\u03b2 (1-42) and prevents LTP deficits in middle-aged mice","volume":"13","author":"S\u00fcdkamp","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.neuron.2015.10.037","article-title":"Synaptic integration of adult-born hippocampal neurons is locally controlled by astrocytes","volume":"88","author":"Sultan","year":"2015","journal-title":"Neuron"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrneurol.2015.119","article-title":"Clearance systems in the brain-implications for Alzheimer disease. In: nature reviews","volume":"11","author":"Tarasoff-Conway","year":"2015","journal-title":"Neurology"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/nature05028","article-title":"NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus","volume":"442","author":"Tashiro","year":"2006","journal-title":"Nature"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"3252","DOI":"10.1523\/JNEUROSCI.4941-06.2007","article-title":"Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage","volume":"27","author":"Tashiro","year":"2007","journal-title":"J. Neurosci."},{"key":"ref79","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4939-1096-0_14","article-title":"Acute brain slice methods for adult and aging animals: application of targeted patch clamp analysis and Optogenetics","volume-title":"Patch-clamp methods and protocols. Methods in molecular biology","author":"Ting","year":"2014"},{"key":"ref1006","doi-asserted-by":"publisher","first-page":"10067","DOI":"10.1523\/JNEUROSCI.22-23-10067.2002","article-title":"Experience-Dependent Coincident Expression of the Effector Immediate-Early Genes Arc and Homer 1a in Hippocampal and Neocortical Neuronal Networks","volume":"22","author":"Vazdarjanova","year":"2002","journal-title":"JNeurosci"},{"key":"ref1013","doi-asserted-by":"publisher","first-page":"20130595","DOI":"10.1098\/rstb.2013.0595","article-title":"Astroglial cradle in the life of the synapse","volume":"369","author":"Verkhratsky","year":"2014","journal-title":"Philos Trans R Soc Lond B Biol Sci."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00441-011-1196-4","article-title":"Immunohistological markers for proliferative events, gliogenesis, and neurogenesis within the adult hippocampus","volume":"345","author":"von Bohlen und Halbach","year":"2011","journal-title":"Cell Tissue Res."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/416535a","article-title":"Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo","volume":"416","author":"Walsh","year":"2002","journal-title":"Nature"},{"key":"ref1004","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1111\/j.1471-4159.2006.04426.x","article-title":"A\u03b2 Oligomers \u2013 a decade of discovery","volume":"101","author":"Walsh","year":"2007","journal-title":"JNeurochemistry"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nature10243","article-title":"Neuronal basis of age-related working memory decline","volume":"476","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1212\/WNL.0000000000001903","article-title":"Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease","volume":"85","author":"Wang","year":"2015","journal-title":"Neurology"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nm838","article-title":"Adult mouse astrocytes degrade amyloid-\u03b2 in vitro and in situ","volume":"9","author":"Wyss-Coray","year":"2003","journal-title":"Nat. Med."},{"key":"ref1015","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.neuropharm.2018.03.007","article-title":"Rhynchophylline suppresses soluble A\u03b21-42-induced impairment of spatial cognition function via inhibiting excessive activation of extrasynaptic NR2B-containing NMDA receptors","volume":"35","author":"Yang","year":"2018","journal-title":"Neuropharmacology."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.tins.2015.04.003","article-title":"Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker","volume":"38","author":"Yang","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1042\/AN20110025","article-title":"Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer\u2019s disease","volume":"3","author":"Yeh","year":"2011","journal-title":"ASN Neuro"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.neulet.2006.04.065","article-title":"Amyloid-beta1\u201342 reduces neuronal excitability in mouse dentate gyrus","volume":"403","author":"Yun","year":"2006","journal-title":"Neurosci. 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