{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:51:24Z","timestamp":1777395084986,"version":"3.51.4"},"reference-count":67,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:p>Background: A decline of brain serotonin (5-HT) is held responsible for the changes in mood that can be observed in Alzheimer\u2019s disease (AD). However, 5-HT\u2019ergic signaling is also suggested to reduce the production of pathogenic amyloid-\u03b2 (A\u03b2). Objective: To investigate the effect of targeted inactivation of tryptophan hydroxylase-2 (Tph2), which is essential for neuronal 5-HT synthesis, on amyloidosis in amyloid precursor protein (APP)swe\/presenilin 1 (PS1) \u0394E9 transgenic mice. Methods: Triple-transgenic (3xTg) APP\/PS1 mice with partial (+\/-) or complete Tph2 knockout (\u2013\/\u2013) were allowed to survive until 6 months old with APP\/PS1, Tph2\u2013\/\u2013, and wildtype mice. Survival and weight were recorded. Levels of A\u03b242\/40\/38, soluble APP\u03b1 (sA\u03b2PP\u03b1) and sA\u03b2PP\u03b2, and cytokines were analyzed by mesoscale, neurotransmitters by mass spectrometry, and gene expression by quantitative PCR. Tph2, microglia, and A\u03b2 were visualized histologically. Results: Tph2 inactivation in APP\/PS1 mice significantly reduced viability, without impacting soluble and insoluble A\u03b242 and A\u03b240 in neocortex and hippocampus, and with only mild changes of soluble A\u03b242\/A\u03b240. However, sA\u03b2PP\u03b1 and sA\u03b2PP\u03b2 in hippocampus and A\u03b238 and A\u03b240 in cerebrospinal fluid were reduced. 3xTg\u2013\/\u2013mice were devoid of Tph2 immunopositive fibers and 5-HT. Cytokines were unaffected by genotype, as were neocortical TNF, HTR2a and HTR2b mRNA levels in Tph2\u2013\/\u2013 mice. Microglia clustered around A\u03b2 plaques regardless of genotype. Conclusion: The results suggest that Tph2 inactivation influences A\u03b2PP processing, at least in the hippocampus, although levels of A\u03b2 are unchanged. The reduced viability of 3xTg\u2013\/\u2013mice could indicate that 5-HT protects against the seizures that can impact the viability of APP\/PS1 mice.<\/jats:p>","DOI":"10.3233\/jad-210581","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T12:08:46Z","timestamp":1639742926000},"page":"1283-1300","source":"Crossref","is-referenced-by-count":12,"title":["The Combined Effects of Amyloidosis and Serotonin Deficiency by Tryptophan Hydroxylase-2 Knockout Impacts Viability of the APP\/PS1 Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"85","author":[{"given":"Christian Ulrich","family":"von Linstow","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark"},{"name":"Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Waider","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne Skov-Skov","family":"Bergh","sequence":"additional","affiliation":[{"name":"Section for Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Anzalone","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark"},{"name":"BRIDGE - Brain Research-Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilie","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark"},{"name":"BRIDGE - Brain Research-Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aina Battle","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Wirenfeldt","sequence":"additional","affiliation":[{"name":"BRIDGE - Brain Research-Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense C, Denmark"},{"name":"Department of Pathology, Institute of Clinical Science, Odense University Hospital, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus-Peter","family":"Lesch","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, W\u00fcrzburg, Germany"},{"name":"Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia"},{"name":"Department of Neuropsychology and Psychiatry, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bente","family":"Finsen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark"},{"name":"BRIDGE - Brain Research-Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-210581_ref1","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1056\/NEJM198110223051714","article-title":"Treatment of Alzheimer\u2019s disease: A cautionary note","volume":"305","author":"Bowen","year":"1981","journal-title":"N Engl J Med"},{"key":"10.3233\/JAD-210581_ref2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0306-4522(91)90198-W","article-title":"Cell loss and nuclear hypertrophy in topographical subdivisions of the nucleus basalis of Meynert in Alzheimer\u2019s disease","volume":"41","author":"Iraizoz","year":"1991","journal-title":"Neuroscience"},{"key":"10.3233\/JAD-210581_ref3","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1007\/BF00227741","article-title":"Brain stem serotonin-synthesizing neurons in Alzheimer\u2019s disease: A clinicopathological correlation","volume":"84","author":"Halliday","year":"1992","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-210581_ref4","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1176\/appi.ajp.161.6.1096","article-title":"Neuropathological study of the dorsal raphe nuclei in late-life depression and Alzheimer\u2019s disease with and without depression","volume":"161","author":"Hendricksen","year":"2004","journal-title":"Am J Psychiatry"},{"key":"10.3233\/JAD-210581_ref5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0006-8993(90)90342-9","article-title":"Evidence for decreased transport of tryptophan hydroxylase in Alzheimer\u2019s disease","volume":"537","author":"Burke","year":"1990","journal-title":"Brain Res"},{"key":"10.3233\/JAD-210581_ref6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1056\/NEJM198507043130102","article-title":"Neurochemical studies of early-onset Alzheimer\u2019s disease. Possible influence on treatment","volume":"313","author":"Francis","year":"1985","journal-title":"N Engl J Med"},{"key":"10.3233\/JAD-210581_ref7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0006-8993(87)91408-9","article-title":"Monoaminergic innervation of the frontal and temporal lobes in Alzheimer\u2019s disease","volume":"401","author":"Palmer","year":"1987","journal-title":"Brain Res"},{"key":"10.3233\/JAD-210581_ref8","first-page":"11","article-title":"Relationship of brain tryptophan and serotonin in improving cognitive performance in rats","volume":"19","author":"Khaliq","year":"2006","journal-title":"Pak J Pharm Sci"},{"key":"10.3233\/JAD-210581_ref9","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1365-2990.2009.01038.x","article-title":"Does Alzheimer\u2019s disease begin in the brainstem?","volume":"35","author":"Simic","year":"2009","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10.3233\/JAD-210581_ref10","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/ageing\/afw053","article-title":"The effect of treatment with selective serotonin reuptake inhibitors in comparison to placebo in the progression of dementia: A systematic review and meta-analysis","volume":"45","author":"Jones","year":"2016","journal-title":"Age Ageing"},{"key":"10.3233\/JAD-210581_ref11","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1159\/000121334","article-title":"Is antidepressant treatment associated with reduced cognitive decline in Alzheimer\u2019s disease?","volume":"25","author":"Mossello","year":"2008","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-210581_ref12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jad.2008.11.020","article-title":"Antidepressants and dementia","volume":"117","author":"Kessing","year":"2009","journal-title":"J Affect Disord"},{"key":"10.3233\/JAD-210581_ref13","doi-asserted-by":"crossref","first-page":"14968","DOI":"10.1073\/pnas.1107411108","article-title":"Serotonin signaling is associated with lower amyloid-\u03b2 levels and plaques in transgenic mice and humans","volume":"108","author":"Cirrito","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-210581_ref14","first-page":"236re234","article-title":"An antidepressant decreases CSF A\u03b2; production in healthy individuals and in transgenic AD mice","volume":"6","author":"Sheline","year":"2014","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-210581_ref15","doi-asserted-by":"crossref","first-page":"268le265","DOI":"10.1126\/scitranslmed.3010053","article-title":"Comment on \u201cAn antidepressant decreases CSF A\u03b2 production in healthy individuals and in transgenic AD mice\u201d","volume":"6","author":"Emilsson","year":"2014","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-210581_ref16","doi-asserted-by":"crossref","first-page":"e2666","DOI":"10.1212\/WNL.0000000000010733","article-title":"Effect of escitalopram on A\u03b2 levels and plaque load in an Alzheimer mouse model","volume":"95","author":"Cirrito","year":"2020","journal-title":"Neurology"},{"key":"10.3233\/JAD-210581_ref17","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.expneurol.2007.01.037","article-title":"Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice","volume":"205","author":"Nelson","year":"2007","journal-title":"Exp Neurol"},{"key":"10.3233\/JAD-210581_ref18","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/j.1474-9726.2012.00845.x","article-title":"High tryptophan diet reduces CA1 intraneuronal \u03b2-amyloid in the triple transgenic mouse model of Alzheimer\u2019s disease","volume":"11","author":"Noristani","year":"2012","journal-title":"Aging Cell"},{"key":"10.3233\/JAD-210581_ref19","doi-asserted-by":"crossref","first-page":"e0165144","DOI":"10.1371\/journal.pone.0165144","article-title":"Behavioural phenotyping of APPswe\/PS1\u03b4E9 mice: Age-related changes and effect of long-term paroxetine treatment","volume":"11","author":"Olesen","year":"2016","journal-title":"PLoS One"},{"key":"10.3233\/JAD-210581_ref20","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.trci.2018.04.005","article-title":"Established amyloid-\u03b2 pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine","volume":"4","author":"Severino","year":"2018","journal-title":"Alzheimers Dementia (N Y)"},{"key":"10.3233\/JAD-210581_ref21","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13195-017-0298-y","article-title":"Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-\u03b2 levels in early-stage Alzheimer\u2019s-like disease in mice","volume":"9","author":"von Linstow","year":"2017","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-210581_ref22","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1176\/appi.ajp.157.4.638","article-title":"Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer\u2019s disease","volume":"157","author":"Porter","year":"2000","journal-title":"Am J Psychiatry"},{"key":"10.3233\/JAD-210581_ref23","doi-asserted-by":"crossref","first-page":"e79947","DOI":"10.1371\/journal.pone.0079947","article-title":"Specific serotonergic denervation affects tau pathology and cognition without altering senile plaques deposition in APP\/PS1 mice","volume":"8","author":"Ramos-Rodriguez","year":"2013","journal-title":"PloS One"},{"key":"10.3233\/JAD-210581_ref24","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00702-008-0096-6","article-title":"Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice","volume":"115","author":"Gutknecht","year":"2008","journal-title":"J Neural Transm (Vienna)"},{"key":"10.3233\/JAD-210581_ref25","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.euroneuro.2008.12.005","article-title":"Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: Convergent data from Tph2 knockout mice","volume":"19","author":"Gutknecht","year":"2009","journal-title":"Eur Neuropsychopharmacol"},{"key":"10.3233\/JAD-210581_ref26","doi-asserted-by":"crossref","first-page":"e43157","DOI":"10.1371\/journal.pone.0043157","article-title":"Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification","volume":"7","author":"Gutknecht","year":"2012","journal-title":"PLoS One"},{"key":"10.3233\/JAD-210581_ref27","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/mp.2011.50","article-title":"Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice","volume":"17","author":"Jacobsen","year":"2012","journal-title":"Mol Psychiatry"},{"key":"10.3233\/JAD-210581_ref28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.neuropharm.2014.05.015","article-title":"Adaptive changes in serotonin metabolism preserve normal behavior in mice with reduced TPH2 activity","volume":"85","author":"Mosienko","year":"2014","journal-title":"Neuropharmacology"},{"key":"10.3233\/JAD-210581_ref29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/hmg\/ddh019","article-title":"Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: Evidence for augmentation of a 42-specific gamma secretase","volume":"13","author":"Jankowsky","year":"2004","journal-title":"Hum Mol Genet"},{"key":"10.3233\/JAD-210581_ref30","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jchromb.2016.06.011","article-title":"Validated methods for determination of neurotransmitters and metabolites in rodent brain tissue and extracellular fluid by reversed phase UHPLC-MS\/MS","volume":"1028","author":"Bergh","year":"2016","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"10.3233\/JAD-210581_ref31","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bbi.2015.03.006","article-title":"Cytokine-producing microglia have an altered beta-amyloid load in aged APP\/PS1 Tg mice","volume":"48","author":"Babcock","year":"2015","journal-title":"Brain Behav Immun"},{"key":"10.3233\/JAD-210581_ref32","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1523\/JNEUROSCI.5505-08.2009","article-title":"Microglia protect neurons against ischemia by synthesis of tumor necrosis factor","volume":"29","author":"Lambertsen","year":"2009","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-210581_ref33","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/glia.20405","article-title":"Tumor necrosis factor and its p55 and p75 receptors are not required for axonal lesion-induced microgliosis in mouse fascia dentata","volume":"54","author":"Fenger","year":"2006","journal-title":"Glia"},{"key":"10.3233\/JAD-210581_ref34","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.bbi.2011.12.002","article-title":"Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity","volume":"26","author":"Krabbe","year":"2012","journal-title":"Brain Behav Immun"},{"key":"10.3233\/JAD-210581_ref35","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/glia.23918","article-title":"The serotonin 2B receptor is required in neonatal microglia to limit neuroinflammation and sickness behavior in adulthood","volume":"69","author":"B\u00e9chade","year":"2021","journal-title":"Glia"},{"key":"10.3233\/JAD-210581_ref36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13024-016-0112-5","article-title":"Redundant Gs-coupled serotonin receptors regulate amyloid-\u03b2 metabolism in vivo","volume":"11","author":"Fisher","year":"2016","journal-title":"Mol Neurodegener"},{"key":"10.3233\/JAD-210581_ref37","doi-asserted-by":"crossref","first-page":"13805","DOI":"10.1523\/JNEUROSCI.4218-08.2008","article-title":"Amyloid pathology is associated with progressive monoaminergic neurodegeneration in a transgenic mouse model of Alzheimer\u2019s disease","volume":"28","author":"Liu","year":"2008","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-210581_ref38","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1098\/rsbl.2006.0495","article-title":"Thermally induced torpor in fullterm lizard embryos synchronizes hatching with ambient conditions","volume":"2","author":"Radder","year":"2006","journal-title":"Biol Lett"},{"key":"10.3233\/JAD-210581_ref39","doi-asserted-by":"crossref","first-page":"2324.e2321","DOI":"10.1016\/j.neurobiolaging.2010.08.014","article-title":"Early onset amyloid lesions lead to severe neuritic abnormalities and local, but not global neuron loss in APPPS1 transgenic mice","volume":"32","author":"Rupp","year":"2011","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-210581_ref40","doi-asserted-by":"crossref","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":"10.3233\/JAD-210581_ref41","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1474-4422(17)30044-3","article-title":"Epileptic activity in Alzheimer\u2019s disease: Causes and clinical relevance","volume":"16","author":"Vossel","year":"2017","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-210581_ref42","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.3389\/fneur.2019.01151","article-title":"Characterization of epileptic spiking associated with brain amyloidosis in APP\/PS1 mice","volume":"10","author":"Gureviciene","year":"2019","journal-title":"Front Neurol"},{"key":"10.3233\/JAD-210581_ref43","doi-asserted-by":"crossref","first-page":"10332","DOI":"10.1073\/pnas.0810793106","article-title":"Growth retardation and altered autonomic control in mice lacking brain serotonin","volume":"106","author":"Alenina","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-210581_ref44","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.neuron.2012.09.013","article-title":"Serotonin in the modulation of neural plasticity and networks: Implications for neurodevelopmental disorders","volume":"76","author":"Lesch","year":"2012","journal-title":"Neuron"},{"key":"10.3233\/JAD-210581_ref45","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1460-9568.2007.05661.x","article-title":"Embryonic depletion of serotonin affects cortical development","volume":"26","author":"Vitalis","year":"2007","journal-title":"Eur J Neurosci"},{"key":"10.3233\/JAD-210581_ref46","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/0014-4886(88)90154-9","article-title":"Effect of 5-hydroxytryptamine on the rate of cerebrospinal fluid production in rabbit","volume":"99","author":"Lindvall-Axelsson","year":"1988","journal-title":"Exp Neurol"},{"key":"10.3233\/JAD-210581_ref47","doi-asserted-by":"crossref","first-page":"C611","DOI":"10.1152\/ajpcell.00292.2003","article-title":"Kv1.1 and Kv1.3 channels contribute to the delayed-rectifying K+ conductance in rat choroid plexus epithelial cells","volume":"286","author":"Speake","year":"2004","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.3233\/JAD-210581_ref48","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3389\/fnmol.2017.00299","article-title":"The serotonin receptor subtype 5b specifically interacts with serotonin receptor subtype 1A","volume":"10","author":"Niebert","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"10.3233\/JAD-210581_ref49","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1074\/jbc.271.8.4188","article-title":"Serotonin 5-HT2a and 5-HT2c receptors stimulate amyloid precursor protein ectodomain secretion","volume":"271","author":"Nitsch","year":"1996","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-210581_ref50","doi-asserted-by":"crossref","first-page":"44881","DOI":"10.1074\/jbc.M109008200","article-title":"The human serotonin 5-HT4 receptor regulates secretion of non-amyloidogenic precursor protein","volume":"276","author":"Robert","year":"2001","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-210581_ref51","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0006-8993(02)03153-0","article-title":"Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs","volume":"951","author":"Arjona","year":"2002","journal-title":"Brain Res"},{"key":"10.3233\/JAD-210581_ref52","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0531-5565(02)00157-2","article-title":"The serotonin 5-HT4 receptor and the amyloid precursor protein processing","volume":"38","author":"Lezoualc\u2019h","year":"2003","journal-title":"Exp Gerontol"},{"key":"10.3233\/JAD-210581_ref53","doi-asserted-by":"crossref","first-page":"e87014","DOI":"10.1371\/journal.pone.0087014","article-title":"Regulation of amyloid precursor protein processing by serotonin signaling","volume":"9","author":"Pimenova","year":"2014","journal-title":"PLoS One"},{"key":"10.3233\/JAD-210581_ref54","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1192\/bjp.178.5.448","article-title":"Effects of rapid tryptophan depletion on brain 5-HT(2) receptors: A PET study","volume":"178","author":"Yatham","year":"2001","journal-title":"Br J Psychiatry"},{"key":"10.3233\/JAD-210581_ref55","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s00213-006-0635-5","article-title":"Acute and chronic tryptophan depletion differentially regulate central 5-HT1A and 5-HT 2A receptor binding in the rat","volume":"190","author":"Cahir","year":"2007","journal-title":"Psychopharmacol (Berl)"},{"key":"10.3233\/JAD-210581_ref56","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.nbd.2004.04.010","article-title":"Late onset loss of hippocampal 5-HT and NE is accompanied by increases in BDNF protein expression in mice co-expressing mutant APP and PS1","volume":"16","author":"Szapacs","year":"2004","journal-title":"Neurobiol Dis"},{"key":"10.3233\/JAD-210581_ref57","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.neuint.2017.04.008","article-title":"Effect of aging and Alzheimer\u2019s disease-like pathology on brain monoamines in mice","volume":"108","author":"Von Linstow","year":"2017","journal-title":"Neurochem Int"},{"key":"10.3233\/JAD-210581_ref58","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3389\/fncel.2019.00308","article-title":"Microglia express insulin-like growth factor-1 in the hippocampus of aged APP(swe)\/PS1(\u0394E9) transgenic mice","volume":"13","author":"Myhre","year":"2019","journal-title":"Front Cell Neurosci"},{"key":"10.3233\/JAD-210581_ref59","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-210581_ref60","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/ana.20508","article-title":"Amyloid beta 38, 40, and 42 species in cerebrospinal fluid: More of the same?","volume":"58","author":"Schoonenboom","year":"2005","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-210581_ref61","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neuron.2008.02.003","article-title":"Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo","volume":"58","author":"Cirrito","year":"2008","journal-title":"Neuron"},{"key":"10.3233\/JAD-210581_ref62","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.neuron.2005.10.028","article-title":"Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo","volume":"48","author":"Cirrito","year":"2005","journal-title":"Neuron"},{"key":"10.3233\/JAD-210581_ref63","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nrn3880","article-title":"Immune attack: The role of inflammation in Alzheimer disease","volume":"16","author":"Heppner","year":"2015","journal-title":"Nat Rev Neurosci"},{"key":"10.3233\/JAD-210581_ref64","doi-asserted-by":"crossref","first-page":"870","DOI":"10.2174\/1567205014666170317113606","article-title":"Impact of cytokines and chemokines on Alzheimer\u2019s disease neuropathological hallmarks","volume":"14","author":"Domingues","year":"2017","journal-title":"Curr Alzheimer Res"},{"key":"10.3233\/JAD-210581_ref65","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of Alzheimer\u2019s disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"10.3233\/JAD-210581_ref66","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3389\/fncel.2018.00397","article-title":"Diverse protein profiles in CNS myeloid cells and CNS tissue from lipopolysaccharide- and vehicle-injected APPSWE\/PS1DeltaE9 transgenic mice implicate cathepsin Z in Alzheimer\u2019s disease","volume":"12","author":"Thygesen","year":"2018","journal-title":"Front Cell Neurosci"},{"key":"10.3233\/JAD-210581_ref67","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s00401-021-02263-w","article-title":"Distinct amyloid-beta and tau-associated microglia profiles in Alzheimer\u2019s disease","volume":"141","author":"Gerrits","year":"2021","journal-title":"Acta Neuropathol"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-210581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:04:54Z","timestamp":1777370694000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-210581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,1]]},"references-count":67,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.3233\/jad-210581","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,1]]}}}