Key Publications

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Publications (Full List)

Link to publications on Pubmed

Hettinger JC, Lee H, Bu G, Holtzman DM, Cirrito JR (2018) AMPA-ergic regulation of amyloid-beta levels in an Alzheimer's disease mouse model. Mol            Neurodegener 13:22.

Czirr E, Castello NA, Mosher KI, Castellano JM, Hinkson IV, Lucin KM, Baeza-Raja B, Ryu JK, Li L, Farina SN, Belichenko NP, Longo FM, Akassoglou K, Britschgi M, Cirrito JR, Wyss-Coray T (2017) Microglial complement receptor 3 regulates brain Abeta levels through secreted proteolytic activity. J Exp Med 214:1081-1092.

Liu CC, Hu J, Zhao N, Wang J, Wang N, Cirrito JR, Kanekiyo T, Holtzman DM, Bu G (2017) Astrocytic LRP1 Mediates Brain Abeta Clearance and Impacts Amyloid Deposition. J Neurosci 37:4023-4031.

Bales KR, O'Neill SM, Pozdnyakov N, Pan F, Caouette D, Pi Y, Wood KM, Volfson D, Cirrito JR, Han BH, Johnson AW, Zipfel GJ, Samad TA (2016) Passive immunotherapy targeting amyloid-beta reduces cerebral amyloid angiopathy and improves vascular reactivity. Brain 139:563-577.

Fisher JR, Wallace CE, Tripoli DL, Sheline YI, Cirrito JR (2016) Redundant Gs-coupled serotonin receptors regulate amyloid-beta metabolism in vivo. Mol Neurodegener 11:45.

Hettinger JC, Cirrito JR (2016) Bad Ac-etylated Tau. Neuron 90:205-206.

Liu CC, Zhao N, Yamaguchi Y, Cirrito JR, Kanekiyo T, Holtzman DM, Bu G (2016) Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-beta clearance and aggregation in Alzheimer's disease. Science translational medicine 8:332ra344.

Moore KM, Girens RE, Larson SK, Jones MR, Restivo JL, Holtzman DM, Cirrito JR, Yuede CM, Zimmerman SD, Timson BF (2016) A spectrum of exercise training reduces soluble Abeta in a dose-dependent manner in a mouse model of Alzheimer's disease. Neurobiol Dis 85:218-224.

Sundaram GS, Dhavale DD, Prior JL, Yan P, Cirrito J, Rath NP, Laforest R, Cairns NJ, Lee JM, Kotzbauer PT, Sharma V (2016) Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (Abeta) in Alzheimer's Disease. Scientific reports 6:35636.

Wang Y, Ulland TK, Ulrich JD, Song W, Tzaferis JA, Hole JT, Yuan P, Mahan TE, Shi Y, Gilfillan S, Cella M, Grutzendler J, DeMattos RB, Cirrito JR, Holtzman DM, Colonna M (2016) TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J Exp Med 213:667-675.

Yuede CM, Lee H, Restivo JL, Davis TA, Hettinger JC, Wallace CE, Young KL, Hayne MR, Bu G, Li CZ, Cirrito JR (2016) Rapid in vivo measurement of beta-amyloid reveals biphasic clearance kinetics in an Alzheimer's mouse model. J Exp Med 213:677-685.

Yamamoto K, Tanei Z, Hashimoto T, Wakabayashi T, Okuno H, Naka Y, Yizhar O, Fenno LE, Fukayama M, Bito H, Cirrito JR, Holtzman DM, Deisseroth K, Iwatsubo T (2015) Chronic optogenetic activation augments abeta pathology in a mouse model of Alzheimer disease. Cell reports 11:859-865.

Born HA, Kim JY, Savjani RR, Das P, Dabaghian YA, Guo Q, Yoo JW, Schuler DR, Cirrito JR, Zheng H, Golde TE, Noebels JL, Jankowsky JL (2014) Genetic suppression of transgenic APP rescues Hypersynchronous network activity in a mouse model of Alzeimer's disease. J Neurosci 34:3826-3840.

Fowler SW, Chiang AC, Savjani RR, Larson ME, Sherman MA, Schuler DR, Cirrito JR, Lesne SE, Jankowsky JL (2014) Genetic modulation of soluble Abeta rescues cognitive and synaptic impairment in a mouse model of Alzheimer's disease. J Neurosci 34:7871-7885.

Paganetti P, Antoniello K, Devraj K, Toni N, Kieran D, Madani R, Pihlgren M, Adolfsson O, Froestl W, Schrattenholz A, Liebner S, Havas D, Windisch M, Cirrito JR, Pfeifer A, Muhs A (2014) Increased efflux of amyloid-beta peptides through the blood-brain barrier by muscarinic acetylcholine receptor inhibition reduces pathological phenotypes in mouse models of brain amyloidosis. J Alzheimers Dis 38:767-786.

Roh JH, Jiang H, Finn MB, Stewart FR, Mahan TE, Cirrito JR, Heda A, Snider BJ, Li M, Yanagisawa M, de Lecea L, Holtzman DM (2014) Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer's disease. J Exp Med 211:2487-2496.

Sheline YI, West T, Yarasheski K, Swarm R, Jasielec MS, Fisher JR, Ficker WD, Yan P, Xiong C, Frederiksen C, Grzelak MV, Chott R, Bateman RJ, Morris JC, Mintun MA, Lee JM, Cirrito JR (2014) An antidepressant decreases CSF Abeta production in healthy individuals and in transgenic AD mice. Science translational medicine 6:236re234.

Sundaram GS, Garai K, Rath NP, Yan P, Cirrito JR, Cairns NJ, Moo-Lee J, Sharma V (2014) Characterization of a Brain Permeant Fluorescent Molecule and Visualization of Abeta Parenchymal Plaques, Using Real-Time Multiphoton Imaging in Transgenic Mice. Organic letters.

Xiao Q, Yan P, Ma X, Liu H, Perez R, Zhu A, Gonzales E, Burchett JM, Schuler DR, Cirrito JR, Diwan A, Lee JM (2014) Enhancing astrocytic lysosome biogenesis facilitates abeta clearance and attenuates amyloid plaque pathogenesis. J Neurosci 34:9607-9620.

Yamada K, Holth JK, Liao F, Stewart FR, Mahan TE, Jiang H, Cirrito JR, Patel TK, Hochgrafe K, Mandelkow EM, Holtzman DM (2014) Neuronal activity regulates extracellular tau in vivo. J Exp Med 211:387-393.

DeVos SL, Goncharoff DK, Chen G, Kebodeaux CS, Yamada K, Stewart FR, Schuler DR, Maloney SE, Wozniak DF, Rigo F, Bennett CF, Cirrito JR, Holtzman DM, Miller TM (2013) Antisense reduction of tau in adult mice protects against seizures. J Neurosci 33:12887-12897.

Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM, Brody DL (2013) Amyloid-beta oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol 73:104-119.

Kanekiyo T, Cirrito JR, Liu CC, Shinohara M, Li J, Schuler DR, Shinohara M, Holtzman DM, Bu G (2013) Neuronal clearance of amyloid-beta by endocytic receptor LRP1. J Neurosci 33:19276-19283.

Kraft AW, Hu X, Yoon H, Yan P, Xiao Q, Wang Y, Gil SC, Brown J, Wilhelmsson U, Restivo JL, Cirrito JR, Holtzman DM, Kim J, Pekny M, Lee JM (2013) Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. FASEB J 27:187-198.

Ulrich JD, Burchett JM, Restivo JL, Schuler DR, Verghese PB, Mahan TE, Landreth GE, Castellano JM, Jiang H, Cirrito JR, Holtzman DM (2013) In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis. Mol Neurodegener 8:13.

Bero AW, Bauer AQ, Stewart FR, White BR, Cirrito JR, Raichle ME, Culver JP, Holtzman DM (2012) Bidirectional relationship between functional connectivity and amyloid-beta deposition in mouse brain. J Neurosci 32:4334-4340.

Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE (2012) ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science 335:1503-1506.

Hunter JM, Cirrito JR, Restivo JL, Kinley RD, Sullivan PM, Holtzman DM, Koger D, Delong C, Lin S, Zhao L, Liu F, Bales K, Paul SM (2012) Emergence of a seizure phenotype in aged apolipoprotein epsilon 4 targeted replacement mice. Brain Res 1467:120-132.

Prabhulkar S, Piatyszek R, Cirrito JR, Wu ZZ, Li CZ (2012) Microbiosensor for Alzheimer's disease diagnostics: detection of amyloid beta biomarkers. J Neurochem 122:374-381.

Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Ho K, Yu GQ, Palop JJ, Mucke L (2012) Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc Natl Acad Sci U S A 109:E2895-2903.

Xiao Q, Gil SC, Yan P, Wang Y, Han S, Gonzales E, Perez R, Cirrito JR, Lee JM (2012) Role of phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) in intracellular amyloid precursor protein (APP) processing and amyloid plaque pathogenesis. J Biol Chem 287:21279-21289.

Bero AW, Yan P, Roh JH, Cirrito JR, Stewart FR, Raichle ME, Lee JM, Holtzman DM (2011) Neuronal activity regulates the regional vulnerability to amyloid-beta deposition. Nature neuroscience 14:750-756.

Chang WP, Huang X, Downs D, Cirrito JR, Koelsch G, Holtzman DM, Ghosh AK, Tang J (2011) Beta-secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice. FASEB J 25:775-784.

Cirrito JR, Disabato BM, Restivo JL, Verges DK, Goebel WD, Sathyan A, Hayreh D, D'Angelo G, Benzinger T, Yoon H, Kim J, Morris JC, Mintun MA, Sheline YI (2011) Serotonin signaling is associated with lower amyloid-{beta} levels and plaques in transgenic mice and humans. Proc Natl Acad Sci U S A 108:14968-14973.

Hong S, Quintero-Monzon O, Ostaszewski BL, Podlisny DR, Cavanaugh WT, Yang T, Holtzman DM, Cirrito JR, Selkoe DJ (2011) Dynamic Analysis of Amyloid beta-Protein in Behaving Mice Reveals Opposing Changes in ISF versus Parenchymal Abeta during Age-Related Plaque Formation. J Neurosci 31:15861-15869.

Kou J, Kim H, Pattanayak A, Song M, Lim JE, Taguchi H, Paul S, Cirrito JR, Ponnazhagan S, Fukuchi K (2011) Anti-Amyloid-beta Single-Chain Antibody Brain Delivery Via AAV Reduces Amyloid Load But May Increase Cerebral Hemorrhages in an Alzheimer's Disease Mouse Model. J Alzheimers Dis 27:23-38.

Verges DK, Restivo JL, Goebel WD, Holtzman DM, Cirrito JR (2011) Opposing Synaptic Regulation of Amyloid-beta Metabolism by NMDA Receptors In Vivo. J Neurosci 31:11328-11337.

Yamada K, Cirrito JR, Stewart FR, Jiang H, Finn MB, Holmes BB, Binder LI, Mandelkow EM, Diamond MI, Lee VM, Holtzman DM (2011) In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice. J Neurosci 31:13110-13117.

Schwetye KE, Cirrito JR, Esparza TJ, Mac Donald CL, Holtzman DM, Brody DL (2010) Traumatic brain injury reduces soluble extracellular amyloid-beta in mice: a methodologically novel combined microdialysis-controlled cortical impact study. Neurobiol Dis 40:555-564.

Cao C, Cirrito JR, Lin X, Wang L, Verges DK, Dickson A, Mamcarz M, Zhang C, Mori T, Arendash GW, Holtzman DM, Potter H (2009) Caffeine Suppresses Amyloid-beta Levels in Plasma and Brain of Alzheimer's Disease Transgenic Mice. J Alzheimers Dis 17:681-697.

Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM (2009) Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326:1005-1007.

Steele JW, Kim SH, Cirrito JR, Verges DK, Restivo JL, Westaway D, Fraser P, Hyslop PS, Sano M, Bezprozvanny I, Ehrlich ME, Holtzman DM, Gandy S (2009) Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo. Mol Neurodegener 4:51.

Yan P, Bero AW, Cirrito JR, Xiao Q, Hu X, Wang Y, Gonzales E, Holtzman DM, Lee JM (2009) Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice. J Neurosci 29:10706-10714.

Cirrito J, Stewart F, Menerick S, Holtzman D (2008a) Synaptic Transmission Dynamically Modulates Interstitial Fluid Amyloid-beta Levels. In: Synaptic Plasticity and the Mechanisms of Alzheimer’s Disease (Selkoe, T., Christen, ed), pp 133-144: Springer.

Cirrito JR, Kang JE, Lee J, Stewart FR, Verges DK, Silverio LM, Bu G, Mennerick S, Holtzman DM (2008b) Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo. Neuron 58:42-51.

Han BH, Zhou ML, Abousaleh F, Brendza RP, Dietrich HH, Koenigsknecht-Talboo J, Cirrito JR, Milner E, Holtzman DM, Zipfel GJ (2008) Cerebrovascular dysfunction in amyloid precursor protein transgenic mice: contribution of soluble and insoluble amyloid-beta peptide, partial restoration via gamma-secretase inhibition. J Neurosci 28:13542-13550.

Farris W, Schutz SG, Cirrito JR, Shankar GM, Sun X, George A, Leissring MA, Walsh DM, Qiu WQ, Holtzman DM, Selkoe DJ (2007) Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy. Am J Pathol 171:241-251.

Kang JE, Cirrito JR, Dong H, Csernansky JG, Holtzman DM (2007) Acute stress increases interstitial fluid amyloid-beta via corticotropin-releasing factor and neuronal activity. Proc Natl Acad Sci U S A 104:10673-10678.

Yan P, Hu X, Song H, Yin K, Bateman RJ, Cirrito JR, Xiao Q, Hsu FF, Turk JW, Xu J, Hsu CY, Holtzman DM, Lee JM (2006) Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J Biol Chem 281:24566-24574.

Yin KJ, Cirrito JR, Yan P, Hu X, Xiao Q, Pan X, Bateman R, Song H, Hsu FF, Turk J, Xu J, Hsu CY, Mills JC, Holtzman DM, Lee JM (2006) Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-beta peptide catabolism. J Neurosci 26:10939-10948.

Brendza RP, Bacskai BJ, Cirrito JR, Simmons KA, Skoch JM, Klunk WE, Mathis CA, Bales KR, Paul SM, Hyman BT, Holtzman DM (2005) Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice. J Clin Invest 115:428-433.

Cirrito JR, Deane R, Fagan AM, Spinner ML, Parsadanian M, Finn MB, Jiang H, Prior JL, Sagare A, Bales KR, Paul SM, Zlokovic BV, Piwnica-Worms D, Holtzman DM (2005a) P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J Clin Invest 115:3285-3290.

Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, Holtzman DM (2005b) Synaptic Activity Regulates Interstitial Fluid Amyloid-beta Levels In Vivo. Neuron 48:913-922.

DeMattos RB, Cirrito JR, Parsadanian M, May PC, O'Dell MA, Taylor JW, Harmony JA, Aronow BJ, Bales KR, Paul SM, Holtzman DM (2004) ApoE and Clusterin Cooperatively Suppress Abeta Levels and Deposition. Evidence that ApoE Regulates Extracellular Abeta Metabolism In Vivo. Neuron 41:193-202.

Zerbinatti CV, Wozniak DF, Cirrito J, Cam JA, Osaka H, Bales KR, Zhuo M, Paul SM, Holtzman DM, Bu G (2004) Increased soluble amyloid-{beta} peptide and memory deficits in amyloid model mice overexpressing the low-density lipoprotein receptor-related protein. Proc Natl Acad Sci U S A 101:1075-1080.

Cirrito JR, Holtzman DM (2003) Amyloid beta and Alzheimer disease therapeutics: the devil may be in the details. J Clin Invest 112:321-323.

Cirrito JR, May PC, O'Dell MA, Taylor JW, Parsadanian M, Cramer JW, Audia JE, Nissen JS, Bales KR, Paul SM, DeMattos RB, Holtzman DM (2003) In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J Neurosci 23:8844-8853.

DeMattos RB, Brendza RP, Heuser JE, Kierson M, Cirrito JR, Fryer J, Sullivan PM, Fagan AM, Han X, Holtzman DM, Center for the Study of Nervous System Injury WUSoMSEABSLMOUSA (2001) Purification and characterization of astrocyte-secreted apolipoprotein E and J-containing lipoproteins from wild-type and human apoE transgenic mice. Neurochem Int 39(5-6):415-425.

Han BH, DeMattos RB, Dugan LL, Kim-Han JS, Brendza RP, Fryer JD, Kierson M, Cirrito J, Quick K, Harmony JA, Aronow BJ, Holtzman DM, Center for the Study of Nervous System Injury WUSoMSLMUSA (2001) Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia. Nat Med 7(3):338-343.

Sheehan TP, Cirrito J, Numan MJ, Numan M, Department of Psychology BCMUSAsbe (2000) Using c-Fos immunocytochemistry to identify forebrain regions that may inhibit maternal behavior in rats. Behav Neurosci 114(2):337-352.

Holtzman DM, Bales KR, Wu S, Bhat P, Parsadanian M, Fagan AM, Chang LK, Sun Y, Paul SM (1999) Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease. J Clin Invest 103:R15-R21.

The Cirrito Lab

WashU, Dept. of Neurology

660 South Euclid Ave | Campus Box 8111

cirritoj@wustl.edu | 314.362.1664

www.cirritolab.com