Reversal of Fragile X Phenotypes by Manipulation of AβPP/Aβ Levels in Fmr1KO Mice

Westmark, Cara J.; Westmark, Pamela R.; O'Riordan, Kenneth J.; Ray, Brian C.; Hervey, Crystal M.; Salamat, M. Shahriar; Abozeid, Sara H.; Stein, Kelsey M.; Stodola, Levi A.; Tranfaglia, Michael; Burger, Corinna; Berry-Kravis, Elizabeth M.; Malter, James S.

doi:10.1371/journal.pone.0026549

Cited by 111Genetics and Neurodevelopmental DisordersAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

Reversal of Fragile X Phenotypes by Manipulation of AβPP/Aβ Levels in Fmr1KO Mice

Open access

Westmark, Cara J., Westmark, Pamela R., O'Riordan, Kenneth J., Ray, Brian C., Hervey, Crystal M., Salamat, M. Shahriar, Abozeid, Sara H., Stein, Kelsey M. +5 more·2011·PLoS ONE

DOI 10.1371/journal.pone.0026549PMC PMC3202540

Open this paper in CoChat — free account Open PDF

Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading known genetic cause of autism. Fragile X mental retardation protein (FMRP), which is absent or expressed at substantially reduced levels in FXS, binds to and controls the postsynaptic translation of amyloid β-protein precursor (AβPP) mRNA. Cleavage of AβPP can produce β-amyloid (Aβ), a 39-43 amino acid peptide mis-expressed in Alzheimer's disease (AD) and Down syndrome (DS). Aβ is over-expressed in the brain of Fmr1(KO) mice, suggesting a pathogenic role in FXS. To determine if genetic reduction of AβPP/Aβ rescues characteristic FXS phenotypes, we assessed audiogenic seizures (AGS), anxiety, the ratio of mature versus immature dendritic spines and metabotropic glutamate receptor (mGluR)-mediated long-term depression (LTD) in Fmr1(KO) mice after removal of one App allele. All of these phenotypes were partially or completely reverted to normal. Plasma Aβ(1-42) was significantly reduced in full-mutation FXS males compared to age-matched controls while cortical and hippocampal levels were somewhat increased, suggesting that Aβ is sequestered in the brain. Evolving therapies directed at reducing Aβ in AD may be applicable to FXS and Aβ may serve as a plasma-based biomarker to facilitate disease diagnosis or assess therapeutic efficacy.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0026549

Cites

92 of 92 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Many classic behavioural phenotypes used as preclinical outcome measures are inconsistently observed in Fmr1-knockout mice.
“many of the other classic behavioural phenotypes used as outcome measures in preclinical studies are inconsistently observed in Fmr1-KO mice (such as open field, rotarod, elevated plus-maze, marble burying, self-grooming and most social paradigms).”
From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [65]
Rescue of these behavioural phenotypes has been difficult to consolidate and to use as a guide for clinical studies.
“As a result, the rescue of these behavioural phenotypes has been difficult to consolidate and to use as a guide for clinical studies30,49,56,64,65.”
From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [65]
Genetic reduction of amyloid β-protein precursor in Fmr1 knockout mice rescues characteristic fragile X syndrome phenotypes such as audiogenic seizures, the ratio of mature to immature dendritic spines, and mGluR-long-term depression.
“Genetic reduction of AβPP in Fmr1 KO mice rescues characteristic FXS phenotypes, such as audiogenic seizures, the ratio of mature versus immature dendritic spines, and mGluR-LTD (91).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [91]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · see citing works
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · see citing works
Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685 · see citing works
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Zhang, F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90397-h · Cited by 3,481 · see citing works
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
The mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580 · see citing works
Instability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome
Oberlé, I., Rousseau, F., Heitz, D., Kretz, C., Devys, D., Hanauer, A., Boué, J., Bertheas, M. F., & Mandel, J. L. (1991) · Science · doi:10.1126/science.252.5009.1097 · Cited by 1,499 · see citing works
Altered synaptic plasticity in a mouse model of fragile X mental retardation
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122205699 · Cited by 1,349 · see citing works
Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome
Wisniewski, K. E., Wisniewski, H. M., & Wen, G. Y. (1985) · Annals of Neurology · doi:10.1002/ana.410170310 · Cited by 1,159 · see citing works
Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109 · see citing works
Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,075 · see citing works
Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression.
Huber, K., Kayser, M., & Bear, M. (2000) · Science · doi:10.1126/science.288.5469.1254 · Cited by 1,015 · see citing works
Correction of Fragile X Syndrome in Mice
Dölen, G., Osterweil, E., Rao, B. S. S., Smith, G. B., Auerbach, B. D., Chattarji, S., & Bear, M. F. (2007) · Neuron · doi:10.1016/j.neuron.2007.12.001 · Cited by 979 · see citing works
Soluble Oligomers of Amyloid β Protein Facilitate Hippocampal Long-Term Depression by Disrupting Neuronal Glutamate Uptake
Li, S., Hong, S., Shepardson, N. E., Walsh, D. M., Shankar, G. M., & Selkoe, D. (2009) · Neuron · doi:10.1016/j.neuron.2009.05.012 · Cited by 972 · see citing works
Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers
Lacor, P. N., Buniel, M. C., Chang, L., Fernandez, S. J., Gong, Y., Viola, K. L., Lambert, M. P., Velasco, P. T., Bigio, E. H., Finch, C. E., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3432-04.2004 · Cited by 954 · see citing works
Dendritic Anomalies in Disorders Associated with Mental Retardation
Kaufmann, W. E. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.10.981 · Cited by 733 · see citing works
β-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity
Zheng, H., Jiang, M., Trumbauer, M. E., SIRINATHSINGHJI, D. J. S., Hopkins, R., Smith, D. W., HEAVENS, R. P., Dawson, G. R., Boyce, S., Conner, M. W., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90073-x · Cited by 699 · see citing works
Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety
Thomas, A., Burant, A., Bui, N., Graham, D., Yuva-Paylor, L. A., & Paylor, R. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1466-y · Cited by 698 · see citing works
The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses
Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S., Oostra, B., & Bagni, C. (2003) · Cell · doi:10.1016/s0092-8674(03)00079-5 · Cited by 676 · see citing works
Water-soluble Aβ(N-40, N-42) oligomers in normal and Alzheimer disease brains
Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., & Roher, A. E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4077 · Cited by 618 · see citing works
Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease
Mehta, P. D., Pirttilä, T., Mehta, S. P., Sersen, E. A., Aisen, P. S., & Wisniewski, H. M. (2000) · Archives of Neurology · doi:10.1001/archneur.57.1.100 · Cited by 582 · see citing works
Evidence that fragile X mental retardation protein is a negative regulator of translation
Laggerbauer, B. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.4.329 · Cited by 571 · see citing works
Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium.
(1994) · PubMed · Cited by 565 · see citing works
Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus
Wang, H.-W., Pasternak, J. F., Kuo, H., Ristic, H., Lambert, M. P., Chromy, B., Viola, K. L., Klein, W. L., Stine, W. B., Krafft, G. A., et al. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03058-x · Cited by 527 · see citing works
Analysis of neocortex in three males with the Fragile X syndrome
Hinton, V. J., Brown, W. T., Wisniewski, K., & Rudelli, R. D. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320410306 · Cited by 527 · see citing works
Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP
Yan, Q. J., Rammal, M., Tranfaglia, M., & Bauchwitz, R. P. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.06.004 · Cited by 521 · see citing works
Self-citation
RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice
Miyashiro, K. Y., Beckel-Mitchener, A., Purk, T. P., Becker, K. G., Barret, T., Liu, L., Carbonetto, S., Weiler, I. J., Greenough, W. T., & Eberwine, J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00034-5 · Cited by 495 · see citing works
Critical periods during sensory development
Berardi, N., Pizzorusso, T., & Maffei, L. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)00047-1 · Cited by 490 · see citing works
From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome
Bagni, C., & Greenough, W. T. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1667 · Cited by 475 · see citing works
Pharmacological Rescue of Synaptic Plasticity, Courtship Behavior, and Mushroom Body Defects in a Drosophila Model of Fragile X Syndrome
McBride, S. M. J., Choi, C. H., Wang, Y., Liebelt, D. A., Braunstein, E. M., Ferreiro, D., Sehgal, A., Siwicki, K. K., Dockendorff, T. C., Nguyen, H. T., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.038 · Cited by 473 · see citing works
Deleterious Effects of Amyloid β Oligomers Acting as an Extracellular Scaffold for mGluR5
Renner, M., Lacor, P. N., Velasco, P. T., Xu, J., Contractor, A., Klein, W. L., & Triller, A. (2010) · Neuron · doi:10.1016/j.neuron.2010.04.029 · Cited by 468 · see citing works
Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model
Bilousova, T. V., Dansie, L., Ngo, M., Aye, J., Charles, J. R., Ethell, D. W., & Ethell, I. M. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.061796 · Cited by 465 · see citing works
Plasma Aβ1–40 and Aβ1–42 and the risk of dementia: a prospective case-cohort study
van Oijen, M., Hofman, A., Soares, H. D., Koudstaal, P. J., & Breteler, M. M. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70501-4 · Cited by 458 · see citing works
The fragile X mental retardation protein inhibits translation via interacting with mRNA
Li, Z. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.11.2276 · Cited by 448 · see citing works
Association of Low Plasma Aβ42/Aβ40 Ratios With Increased Imminent Risk for Mild Cognitive Impairment and Alzheimer Disease
Graff‐Radford, N. R., Crook, J. E., Lucas, J. A., Boeve, B. F., Knopman, D. S., Ivnik, R. J., Smith, G. E., Younkin, L. H., Petersen, R. C., & Younkin, S. G. (2007) · Archives of Neurology · doi:10.1001/archneur.64.3.354 · Cited by 441 · see citing works
Block of Long-Term Potentiation by Naturally Secreted and Synthetic Amyloid β-Peptide in Hippocampal Slices Is Mediated via Activation of the Kinases c-Jun N-Terminal Kinase, Cyclin-Dependent Kinase 5, and p38 Mitogen-Activated Protein Kinase as well as Metabotropic Glutamate Receptor Type 5
Wang, Q., Walsh, D. M., Rowan, M. J., Selkoe, D. J., & Anwyl, R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1633-03.2004 · Cited by 437 · see citing works
Plasma Aβ40 and Aβ42 and Alzheimer’s disease: Relation to age, mortality, and risk
Mayeux, R., Honig, L. S., Tang, M.-X., Manly, J., Stern, Y., Schupf, N., & Mehta, P. D. (2003) · Neurology · doi:10.1212/01.wnl.0000091890.32140.8f · Cited by 434 · see citing works
Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses
Almeida, C. G., Tampellini, D., Takahashi, R. H., Greengard, P., Lin, M. T., Snyder, E. M., & Gouras, G. K. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.008 · Cited by 397 · see citing works
Autism Spectrum Phenotype in Males and Females with Fragile X Full Mutation and Premutation
Clifford, S. M., Dissanayake, C., Bui, M., Huggins, R., Taylor, A. K., & Loesch, D. Z. (2006) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-006-0205-z · Cited by 380 · see citing works
Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression
Mazrouï, R. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.24.3007 · Cited by 369 · see citing works
Adult fragile X syndrome: Clinico-neuropathologic findings
Rudelli, R. D., Brown, W. T., Wisniewski, K., Jenkins, E. C., Laure-Kamionowska, M., Connell, F., & Wisniewski, H. M. (1985) · Acta Neuropathologica · doi:10.1007/bf00687814 · Cited by 362 · see citing works
Fragile X mice develop sensory hyperreactivity to auditory stimuli
Chen, L., & Toth, M. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00036-7 · Cited by 345 · see citing works
The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development
Lu, R., Wang, H., Liang, Z., Ku, L., O'Donnell, W. T., Li, W., Warren, S. T., & Feng, Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404995101 · Cited by 322 · see citing works
Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice
de Vrij, F. M. S., Levenga, J., van der Linde, H. C., Koekkoek, S. K., De Zeeuw, C. I., Nelson, D. L., Oostra, B. A., & Willemsen, R. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.04.002 · Cited by 313 · see citing works
Fenobam: A Clinically Validated Nonbenzodiazepine Anxiolytic Is a Potent, Selective, and Noncompetitive mGlu5 Receptor Antagonist with Inverse Agonist Activity
Porter, R. H. P., Jaeschke, G., Spooren, W., Ballard, T. M., Büttelmann, B., Kolczewski, S., Peters, J.-U., Prinssen, E., Wichmann, J., Vieira, E., et al. (2005) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.089839 · Cited by 308 · see citing works
FMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein
Westmark, C. J., & Malter, J. S. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050052 · Cited by 292 · cited 10× · see citing works
“Our preliminary studies indicate a trend for elevated Ab in FXS brain, which agrees with data in Fmr1 mice [11].”
BackgroundMethodResultInfluentialSelf-citation
Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome
Dölen, G., & Bear, M. F. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.150722 · Cited by 278 · see citing works
Evaluation of plasma Aβ40 and Aβ42 as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment
Hansson, O., Zetterberg, H., Vanmechelen, E., Vanderstichele, H., Andréasson, U., Londos, E., Wallin, A., Minthon, L., & Blennow, K. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.03.027 · Cited by 276 · see citing works
Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice.
Frankland, P. W., Wang, Y., Rosner, B., Shimizu, T., Balleine, B. W., Dykens, E. M., Ornitz, E. M., & Silva, A. J. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001432 · Cited by 275 · see citing works
Epilepsy in fragile X syndrome
Berry‐Kravis, E. (2002) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2002.tb00277.x · Cited by 271 · see citing works
Self-citation
The Drosophila β-Amyloid Precursor Protein Homolog Promotes Synapse Differentiation at the Neuromuscular Junction
Torroja, L., Packard, M. C., Gorczyca, M. G., White, K., & Budnik, V. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-18-07793.1999 · Cited by 268 · see citing works
Synaptotrophic effects of human amyloid β protein precursors in the cortex of transgenic mice
Mucke, L., Masliah, E., Johnson, W. B., Ruppe, M. D., Alford, M. F., Rockenstein, E. M., Forss‐Petter, S., Pietropaolo, M., Mallory, M. E., & Abraham, C. R. (1994) · Brain Research · doi:10.1016/0006-8993(94)90767-6 · Cited by 265 · see citing works
The fra(X) syndrome: Neurological, electrophysiological, and neuropathological abnormalities
Wisniewski, K. E., Segan, S. M., Miezejeski, C. M., Sersen, E. A., & Rudelli, R. D. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320380267 · Cited by 261 · see citing works
Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses
Antar, L. N., Li, C., Zhang, H., Carroll, R. C., & Bassell, G. J. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.02.001 · Cited by 259 · see citing works
Epilepsy and EEG Findings in Males with Fragile X Syndrome
Musumeci, S. A., Hagerman, R. J., Ferri, R., Bosco, P., Bernardina, B. D., Tassinari, C. A., Sarro, G. D., & Elia, M. (1999) · Epilepsia · doi:10.1111/j.1528-1157.1999.tb00824.x · Cited by 250 · see citing works
Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease
Schupf, N., Tang, M. X., Fukuyama, H., Manly, J., Andrews, H., Mehta, P., Ravetch, J., & Mayeux, R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805902105 · Cited by 225 · see citing works
A phenotypic and molecular characterization of the fmr1‐tm1Cgr Fragile X mouse
Yan, Q. J., Asafo‐Adjei, P. K., Arnold, H. M., Brown, R. E., & Bauchwitz, R. P. (2004) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2004.00087.x · Cited by 213 · see citing works
Comorbidity of autistic spectrum disorders in children with Down syndrome
Kent, L., Evans, J., Paul, M., & Sharp, M. (1999) · Developmental Medicine & Child Neurology · doi:10.1017/s001216229900033x · Cited by 201 · see citing works
Biochemical markers in persons with preclinical familial Alzheimer disease
Ringman, J. M., Younkin, S. G., Pratico, D., Seltzer, W., Cole, G. M., Geschwind, D. H., Rodriguez-Agudelo, Y., Schaffer, B., Fein, J., Sokolow, S., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000303973.71803.81 · Cited by 198 · see citing works
Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage.
Hung, A. Y., Koo, E. H., Haass, C., & Selkoe, D. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.20.9439 · Cited by 175 · see citing works
The Amyloid Precursor Protein Is Developmentally Regulated and Correlated with Synaptogenesis
Moya, K. L., Benowitz, L. I., Schneider, G. E., & Allinquant, B. (1994) · Developmental Biology · doi:10.1006/dbio.1994.1055 · Cited by 157 · see citing works
β‐Amyloid Precursor Protein Isoforms in Various Rat Brain Regions and During Brain Development
Löffler, J., & Huber, G. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08443.x · Cited by 150 · see citing works
Minocycline inhibits neuronal death and glial activation induced by β‐amyloid peptide in rat hippocampus
Ryu, J. K., Franciosi, S., Sattayaprasert, P., Kim, S. U., & McLarnon, J. G. (2004) · Glia · doi:10.1002/glia.20051 · Cited by 129 · see citing works
Regulation and Expression of the Alzheimer's β/A4 Amyloid Protein Precursor in Health, Disease, and Down's Syndromea
Beyreuther, K. T., Pollwein, P., Multhaup, G., Mönning, U., KÖNIG, G., Dyrks, T., SCHUBERT, W. J., & Masters, C. L. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb23035.x · Cited by 123 · see citing works
High Levels of Alzheimer Beta-Amyloid Precursor Protein (APP) in Children With Severely Autistic Behavior and Aggression
Sokol, D. K., Chen, D., Farlow, M. R., Dunn, D. W., Maloney, B., Zimmer, J. A., & Lahiri, D. K. (2006) · Journal of Child Neurology · doi:10.1177/08830738060210062201 · Cited by 120 · see citing works
MAPK recruitment by β‐amyloid in organotypic hippocampal slice cultures depends on physical state and exposure time
Bell, K. A., O’Riordan, K. J., Sweatt, J. D., & Dineley, K. T. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02722.x · Cited by 114 · see citing works
Self-citation
Regulation of Nuclear Factor κB in the Hippocampus by Group I Metabotropic Glutamate Receptors
O’Riordan, K. J., Huang, I.-C., Pizzi, M., Spano, P., Boroni, F., Egli, R. E., Desai, P., Fitch, O., Malone, L. M., Ahn, H. J., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4527-05.2006 · Cited by 112 · see citing works
Self-citation
Plasma levels of amyloid β-protein 42 are increased in women with mild cognitive impairment
Assini, A., Cammarata, S., Vitali, A., Colucci, M. E. W., Giliberto, L., Borghi, R., Inglese, M. L., Volpe, S., Ratto, S., Dagna-Bricarelli, F., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000137040.64252.ed · Cited by 104 · see citing works
Elevated Plasma β-Amyloid Peptide Aβ42 Levels, Incident Dementia, and Mortality in Down Syndrome
Schupf, N., Patel, B. N., Pang, D. I., Zigman, W. B., Silverman, W. P., Mehta, P. D., & Mayeux, R. P. (2007) · Archives of Neurology · doi:10.1001/archneur.64.7.1007 · Cited by 100 · see citing works
Inhibitory effect of minocycline on amyloid β fibril formation and human microglial activation
Familian, A., Boshuizen, R. S., Eikelenboom, P., & Veerhuis, R. (2005) · Glia · doi:10.1002/glia.20268 · Cited by 85 · see citing works
Amyloid precursor protein is localized in growing neurites of neonatal rat brain
Masliah, E., Mallory, M. E., Ge, N., & Saitoh, T. (1992) · Brain Research · doi:10.1016/0006-8993(92)91329-d · Cited by 81 · see citing works
Peripheral biomarkers in Autism: secreted amyloid precursor protein-alpha as a probable key player in early diagnosis.
Bailey, A. R., Giunta, B. N., Obregon, D. F., Nikolic, W. V., Tian, J., Sanberg, C. D., Sutton, D. T., & Tan, J. (2008) · PubMed Central · Cited by 74 · see citing works
Early‐phase ERK activation as a biomarker for metabolic status in fragile X syndrome
Weng, N., Weiler, I. J., Sumis, A. M., Berry‐Kravis, E., & Greenough, W. T. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30765 · Cited by 72 · see citing works
Self-citation
Increased amyloid β protein levels in children and adolescents with Down syndrome
Mehta, P. D., Capone, G. T., Jewell, A., & Freedland, R. L. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2006.12.010 · Cited by 69 · see citing works
Mechanism of membrane depolarization caused by the Alzheimer Aβ1–42 peptide
Blanchard, B. J., Thomas, V. L., & Ingram, V. M. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00346-7 · Cited by 66 · see citing works
A null mutation for Fmr1 in female mice: Effects on regional cerebral metabolic rate for glucose and relationship to behavior
Qin, M., Kang, J. Y., & Smith, C. B. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.06.081 · Cited by 64 · see citing works
Plasma levels of Aβ peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer’s disease
Sobów, T., Flirski, M., Kłoszewska, I., & Liberski, P. P. (2005) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2005-1544 · Cited by 62 · see citing works
Comorbidity of autistic spectrum disorders in children with Down syndrome
Kent, L., Evans, J., Paul, M., et al. (1999) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1999.tb00574.x · Cited by 62 · see citing works
Aβ promotes Alzheimer’s disease‐like cytoskeleton abnormalities with consequences to APP processing in neurons
Henriques, A. G., Vieira, S. I., Silva, E. F. D. C. E., & Silva, O. A. B. D. C. E. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06643.x · Cited by 60 · see citing works
Alzheimer's Disease and Down Syndrome Rodent Models Exhibit Audiogenic Seizures
Westmark, C. J., Westmark, P. R., & Malter, J. S. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100087 · Cited by 58 · see citing works
Self-citation
Gene Expression Profiles in a Transgenic Animal Model of Fragile X Syndrome
D’Agata, V., Warren, S. T., Zhao, W., Torre, E. R., Alkon, D. L., & Cavallaro, S. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0506 · Cited by 54 · see citing works
Demonstration of abnormal cyclic AMP production in platelets from patients with fragile X syndrome
Berry‐Kravis, E., & Sklena, P. J. (1993) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320450120 · Cited by 50 · see citing works
Self-citation
Extracellular-regulated kinase controls β-amyloid precursor protein mRNA decay
Westmark, C. J., & Malter, J. S. (2001) · Molecular Brain Research · doi:10.1016/s0169-328x(01)00112-7 · Cited by 36 · see citing works
Self-citation
NADPH oxidase mediates β-amyloid peptide-induced activation of ERK in hippocampal organotypic cultures
Serrano, F., Chang, A., Hernandez, C. M., Pautler, R. G., Sweatt, J. D., & Klann, E. (2009) · Molecular Brain · doi:10.1186/1756-6606-2-31 · Cited by 24 · see citing works
Evaluation of plasma Aβ40 and Aβ42 as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment
Kester, M. I., Verwey, N. A., van Elk, E. J., Scheltens, P., & Blankenstein, M. A. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.07.024 · Cited by 21 · see citing works
β‐Amyloid1–40 Increases Expression of β‐Amyloid Precursor Protein in Neuronal Hybrid Cells
Le, W., Xie, W. J., Nyormoi, O., Ho, B., Smith, R. G., & Appel, S. H. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65052373.x · Cited by 18 · see citing works
Phenyl ureas of creatinine as mGluR5 antagonists. A structure–activity relationship study of fenobam analogues
Wållberg, A., Nilsson, K. A., Österlund, K., Peterson, A., Elg, S., Raboisson, P., Bauer, U., Hammerland, L. G., & Mattsson, J. P. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.11.092 · Cited by 17 · see citing works
Long‐term potentiation in the hippocampus of fragile X knockout mice
Godfraind, J., Reyniers, E., Boulle, K. D., D’Hooge, R., Deyn, P. P. D., Bakker, C. E., Oostra, B. A., Kooy, R. F., & Willems, P. J. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960809)64:2 · Cited by 16 · see citing works
A role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome
Dölen, G., & Bear, M.-F. (2009) · Neuroscience Research · doi:10.1016/j.neures.2009.09.1647 · Cited by 5 · see citing works
Untitled work
Miller (1999) · doi:10.1002/(sici)1096-8628(19990402)83:4
Untitled work
Irwin (2001) · doi:10.1002/1096-8628(20010115)98:2

Flagged first, then by citations

Research works printed but not linked: 2

[1]Hagerman RJ Hagerman PJ 2002 Physical and behavioral phenotype Baltimore John Hopkins University Press 3 109
[69]Miller LJ McIntosh DN McGrath J Shyu V Lampe M 1999 Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: A preliminary report. Am J Med Genet 83 4 268 279 10208160

Sorted by citations

Fragile X syndrome
Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838 · see citing works
Self-citation
The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)
Bhakar, A. L., Dölen, G., & Bear, M. F. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153138 · Cited by 370 · see citing works
Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome
Berry-Kravis, E. M., Lindemann, L., Jønch, A. E., Apostol, G., Bear, M. F., Carpenter, R. L., Crawley, J. N., Curie, A., Des Portes, V., Hossain, F., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.221 · Cited by 336 · see citing works
Self-citation
Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
Bagni, C., Tassone, F., Neri, G., & Hagerman, R. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63141 · Cited by 321 · see citing works
Dysregulation and restoration of translational homeostasis in fragile X syndrome
Richter, J. D., Bassell, G. J., & Klann, E. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4001 · Cited by 275 · see citing works
Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model
Naviaux, J. C., Wang, L., Li, K., Bright, A., Alaynick, W. A., Williams, K. R., Powell, S. B., & Naviaux, R. K. (2015) · Molecular Autism · doi:10.1186/2040-2392-6-1 · Cited by 285 · see citing works
Down syndrome: the brain in trisomic mode
Dierssen, M. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3314 · Cited by 273 · see citing works
Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome
Deidda, G., Parrini, M., Naskar, S., Bozarth, I. F., Contestabile, A., & Cancedda, L. (2015) · Nature Medicine · doi:10.1038/nm.3827 · Cited by 268 · see citing works
Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models
Martínez‐Cerdeño, V. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22417 · Cited by 256 · see citing works
Fragile X mental retardation protein and synaptic plasticity
Sidorov, M. S., Auerbach, B. D., & Bear, M. F. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-15 · Cited by 243 · see citing works
Progress toward treatments for synaptic defects in autism
Delorme, R., Ey, E., Toro, R., Leboyer, M., Gillberg, C., & Bourgeron, T. (2013) · Nature Medicine · doi:10.1038/nm.3193 · Cited by 218 · see citing works
Outcome Measures for Clinical Trials in Fragile X Syndrome
Berry‐Kravis, E., Hessl, D. R., Abbeduto, L., Reiss, A. L., Beckel-Mitchener, A. C., & Urv, T. K. (2013) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e31829d1f20 · Cited by 154 · see citing works
Self-citation
Fragile X syndrome and associated disorders: Clinical aspects and pathology
Salcedo‐Arellano, M. J., Dufour, B. D., McLennan, Y. A., Martínez‐Cerdeño, V., & Hagerman, R. J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104740 · Cited by 141 · see citing works
Pax6-Dependent Cortical Glutamatergic Neuronal Differentiation Regulates Autism-Like Behavior in Prenatally Valproic Acid-Exposed Rat Offspring
Kim, K. C., Lee, D.-K., Go, H. S., Kim, P., Choi, C. S., Kim, J., Jeon, S. J., Song, M., & Shin, C. Y. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8535-2 · Cited by 135 · see citing works
Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease
Hamilton, A., Esseltine, J. L., DeVries, R. A., Cregan, S. P., & Ferguson, S. S. G. (2014) · Molecular Brain · doi:10.1186/1756-6606-7-40 · Cited by 131 · see citing works
Of Men and Mice: Modeling the Fragile X Syndrome
Dahlhaus, R. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00041 · Cited by 118 · see citing works
Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model
Goebel‐Goody, S. M., Wilson‐Wallis, E. D., Royston, S., Tagliatela, S. M., Naegele, J. R., & Lombroso, P. J. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00781.x · Cited by 108 · see citing works
Early-onset network hyperexcitability in presymptomatic Alzheimer’s disease transgenic mice is suppressed by passive immunization with anti-human APP/Aβ antibody and by mGluR5 blockade
Kazim, S. F., Chuang, S.-C., Zhao, W., Wong, R. K. S., Bianchi, R., & Iqbal, K. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00071 · Cited by 109 · see citing works
Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back
Gross, C., Hoffmann, A., Bassell, G. J., & Berry-Kravis, E. M. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0355-9 · Cited by 105 · see citing works
Self-citation
Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models
Doll, C. A., & Broadie, K. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00030 · Cited by 81 · see citing works
Metformin for treatment of fragile X syndrome and other neurological disorders
Gantois, I., Popic, J., Khoutorsky, A., & Sonenberg, N. (2019) · Annual Review of Medicine · doi:10.1146/annurev-med-081117-041238 · Cited by 87 · see citing works
Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach usPreprint
Santos, A. R., Kanellopoulos, A. K., & Bagni, C. (2014) · Learning & Memory · doi:10.1101/lm.035956.114 · Cited by 86 · see citing works
Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model.
Cheng, C., Lau, S. K. M., & Doering, L. C. (2016) · Molecular Brain · doi:10.1186/s13041-016-0256-9 · Cited by 84 · see citing works
Alzheimer’s disease-related dysregulation of mRNA translation causes key pathological features with ageing
Ghosh, A., Mizuno, K., Tiwari, S. S., Proitsi, P., Gomez Perez-Nievas, B., Glennon, E., Martinez-Nunez, R. T., & Giese, K. P. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00882-7 · Cited by 78 · see citing works
Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome
Pasciuto, E., Ahmed, T., Wahle, T., Gardoni, F., D’Andrea, L., Pacini, L., Jacquemont, S., Tassone, F., Balschun, D., Dotti, C. G., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.032 · Cited by 71 · see citing works
Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex
Fatemi, S. H., Folsom, T. D., Kneeland, R. E., Yousefi, M. K., Liesch, S. B., & THURAS, P. D. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-21 · Cited by 69 · see citing works
Audiogenic Seizures in theFmr1Knock-Out Mouse Are Induced byFmr1Deletion in Subcortical, VGlut2-Expressing Excitatory Neurons and Require Deletion in the Inferior Colliculus
Gonzalez, D., Tomasek, M. P., Hays, S. A., Sridhar, V., Ammanuel, S. G., Chang, C.-W., Pawlowski, K. S., Huber, K. M., & Gibson, J. R. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0886-19.2019 · Cited by 64 · see citing works
Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss
Tiwari, S. S., Mizuno, K., Ghosh, A., Aziz, W., Troakes, C., Daoud, J., Golash, V., Noble, W., Hortobágyi, T., & Giese, K. P. (2016) · Brain · doi:10.1093/brain/aww205 · Cited by 65 · see citing works
Rescue of NMDAR-Dependent Synaptic Plasticity in Fmr1 Knock-Out Mice
Bostrom, C. A., Majaess, N. M., Morch, K., White, E. R., Eadie, B. D., & Christie, B. R. (2013) · Cerebral Cortex · doi:10.1093/cercor/bht237 · Cited by 66 · see citing works
What’s hAPPening at synapses? The role of amyloid β-protein precursor and β-amyloid in neurological disorders
Westmark, C. J. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.122 · Cited by 63 · see citing works
Self-citation
Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders
Węgiel, J., Frackowiak, J., Mazur‐Kolecka, B., Schanen, N. C., Cook, E. H., Sigman, M., Brown, W. T., Kuchna, I., Wegiel, J., Nowicki, K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035414 · Cited by 64 · see citing works
Identification of Fragile X Syndrome Specific Molecular Markers in Human Fibroblasts: A Useful Model to Test the Efficacy of Therapeutic Drugs
Kumari, D., Bhattacharya, A., Nadel, J., Moulton, K., Zeak, N. M., Glicksman, A., Dobkin, C., Brick, D. J., Schwartz, P. H., Smith, C. B., et al. (2014) · Human Mutation · doi:10.1002/humu.22699 · Cited by 61 · see citing works
ADAM10 as a therapeutic target for brain diseases: from developmental disorders to Alzheimer’s disease
Marcello, E. E., Borroni, B., Pelucchi, S., Gardoni, F., & Luca, M. D. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1386176 · Cited by 58 · see citing works
Fluorescent labeling of dendritic spines in cell cultures with the carbocyanine dye “DiI”
Cheng, C., Trzcinski, O., & Doering, L. C. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00030 · Cited by 56 · see citing works
Metabotropic Glutamate Receptors in Central Nervous System Diseases
Golubeva, A. V., Moloney, R. D., O’Connor, R. M., Dinan, T. G., & Cryan, J. F. (2016) · Current Drug Targets · doi:10.2174/1389450116666150316224011 · Cited by 49 · see citing works
Neuronal nucleus and cytoplasm volume deficit in children with autism and volume increase in adolescents and adults
Wegiel, J., Flory, M., Kuchna, I., Nowicki, K., Ma, S. Y., Imaki, H., Wegiel, J., Frackowiak, J., Kolecka, B. M., Wierzba-Bobrowicz, T., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0183-5 · Cited by 47 · see citing works
Impact of acamprosate on plasma amyloid-β precursor protein in youth: A pilot analysis in fragile X syndrome-associated and idiopathic autism spectrum disorder suggests a pharmacodynamic protein marker
Erickson, C. A., Ray, B., Maloney, B., Wink, L. K., Bowers, K. A., Schaefer, T. L., McDougle, C. J., Sokol, D. K., & Lahiri, D. K. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.07.011 · Cited by 48 · see citing works
Self-citation
From FMRP Function to Potential Therapies for Fragile X Syndrome
Sethna, F., Moon, C., & Wang, H. (2013) · Neurochemical Research · doi:10.1007/s11064-013-1229-3 · Cited by 47 · see citing works
Multiple drug treatments that increase cAMP signaling restore long-term memory and aberrant signaling in fragile X syndrome models
Choi, C. H., Schoenfeld, B. P., Bell, A. J., Hinchey, J., Rosenfelt, C., Gertner, M. J., Campbell, S. R., Emerson, D., Hinchey, P., Kollaros, M., et al. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00136 · Cited by 46 · see citing works
The potential role of melatonin on sleep deprivation-induced cognitive impairments: Implication of FMRP on cognitive function
Kwon, K. J., Lee, E., Kim, M. K., Jeon, S., Choi, Y. Y., Shin, C. Y., & Han, S. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.079 · Cited by 46 · see citing works
Novel roles of amyloid-beta precursor protein metabolites in fragile X syndrome and autism
Westmark, C. J., Sokol, D. K., Maloney, B., & Lahiri, D. K. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.134 · Cited by 45 · see citing works
Self-citation
Bryostatin-1 Restores Hippocampal Synapses and Spatial Learning and Memory in Adult Fragile X Mice
Sun, M., Hongpaisan, J., Lim, C. S., & Alkon, D. L. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.214098 · Cited by 44 · see citing works
Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis
Khalfallah, O., Jarjat, M., Davidovic, L., Nottet, N., Cestèle, S., Mantegazza, M., & Bardoni, B. (2016) · Stem Cells · doi:10.1002/stem.2505 · Cited by 44 · see citing works
Emerging pharmacologic treatment options for fragile X syndrome
Erickson, C. A., Schaefer, T. L., & Davenport, M. H. (2015) · The Application of Clinical Genetics · doi:10.2147/tacg.s35673 · Cited by 43 · see citing works
Finding novel distinctions between the sAPPα-mediated anabolic biochemical pathways in Autism Spectrum Disorder and Fragile X Syndrome plasma and brain tissue
Ray, B., Sokol, D. K., Maloney, B., & Lahiri, D. K. (2016) · Scientific Reports · doi:10.1038/srep26052 · Cited by 42 · see citing works
Self-citation
Soy-Based Diet Exacerbates Seizures in Mouse Models of Neurological Disease
Westmark, C. J., Westmark, P. R., & Malter, J. S. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121426 · Cited by 41 · see citing works
Self-citation
Opposite Dysregulation of Fragile-X Mental Retardation Protein and Heteronuclear Ribonucleoprotein C Protein Associates with Enhanced APP Translation in Alzheimer Disease
Borreca, A., Gironi, K., Amadoro, G., & Ammassari‐Teule, M. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9229-8 · Cited by 41 · see citing works
Persistent astrocyte activation in the fragile <scp>X</scp> mouse cerebellum
Pacey, L. K. K., Guan, S., Tharmalingam, S., Thomsen, C., & Hampson, D. R. (2015) · Brain and Behavior · doi:10.1002/brb3.400 · Cited by 39 · see citing works
Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex
Yetman, M. J., Lillehaug, S., Bjaalie, J. G., Leergaard, T. B., & Jankowsky, J. L. (2015) · Brain Structure and Function · doi:10.1007/s00429-015-1040-9 · Cited by 34 · see citing works
Molecular Biomarkers in Fragile X Syndrome
Zafarullah, M., & Tassone, F. (2019) · Brain Sciences · doi:10.3390/brainsci9050096 · Cited by 36 · see citing works
Fragile X syndrome neurobiology translates into rational therapy
Braat, S., & Kooy, R. F. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.01.013 · Cited by 32 · see citing works
Integrated transcriptome analysis of human iPS cells derived from a fragile X syndrome patient during neuronal differentiation
Lü, P., Chen, X., Feng, Y., Zeng, Q., Jiang, C., Zhu, X., Fan, G., & Xue, Z. (2016) · Science China Life Sciences · doi:10.1007/s11427-016-0194-6 · Cited by 32 · see citing works
Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors
Xu, J., Marshall, J. J., Kraniotis, S., Nomura, T., Zhu, Y., & Contractor, A. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113378 · Cited by 34 · see citing works
Sleep deficiency as a driver of cellular stress and damage in neurological disorders
Coulson, R. L., Mourrain, P., & Wang, G. X. (2022) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2022.101616 · Cited by 32 · see citing works
MicroRNA-323-3p with clinical potential in rheumatoid arthritis, Alzheimer's disease and ectopic pregnancy
Xu, T., Li, L., Huang, C., Li, X., Peng, Y., & Li, . (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.855201 · Cited by 32 · see citing works
Fragile X and APP: a Decade in Review, a Vision for the Future
Westmark, C. J. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1344-x · Cited by 31 · see citing works
Self-citation
The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17
Zheng, Y., Verhoeff, T. A., Perez‐Pardo, P., Garssen, J., & Kraneveld, A. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010118 · Cited by 31 · see citing works
Mouse models of fragile X-related disorders
Willemsen, R., & Kooy, R. F. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.049485 · Cited by 27 · see citing works
Long-term Continuous EEG Monitoring in Small Rodent Models of Human Disease Using the Epoch Wireless Transmitter System
Zayachkivsky, A., Lehmkuhle, M. J., & Dudek, F. E. (2015) · Journal of Visualized Experiments · doi:10.3791/52554 · Cited by 26 · see citing works
Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes
Wang, H., Pati, S. B. B., Pozzo‐Miller, L. D., & Doering, L. C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00055 · Cited by 25 · see citing works
Preclinical testing of the ketogenic diet in fragile X mice
Westmark, P. R., Gutierrez, A., Gholston, A. K., Wilmer, T. M., & Westmark, C. J. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104687 · Cited by 25 · see citing works
Self-citation
APP Causes Hyperexcitability in Fragile X Mice
Westmark, C. J., Chuang, S.-C., Hays, S. A., Filon, M. J., Ray, B. C., Westmark, P. R., Gibson, J. R., Huber, K. M., & Wong, R. K. S. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00147 · Cited by 24 · see citing works
Self-citation
Transcriptional and Post-Transcriptional Regulations of Amyloid-β Precursor Protein (APP) mRNA
Sato, K., Takayama, K., Hashimoto, M., & Inoue, S. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.721579 · Cited by 24 · see citing works
Fragile X mental retardation protein expression in Alzheimer’s disease
Renoux, A. J., Carducci, N. M., Ahmady, A. A., & Todd, P. K. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00360 · Cited by 23 · see citing works
Fragile X mental retardation protein: from autism to neurodegenerative disease
Wang, H. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00043 · Cited by 23 · see citing works
An “Omic” Overview of Fragile X Syndrome
Dionne, O., & Corbin, F. (2021) · Biology · doi:10.3390/biology10050433 · Cited by 22 · see citing works
The regulation of AβPP expression by RNA-binding proteins
Westmark, C. J., & Malter, J. S. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.03.005 · Cited by 21 · see citing works
Self-citation
AAV‐delivered diacylglycerol kinase DGKk achieves long‐term rescue of fragile X syndrome mouse model
Habbas, K., Cakil, O., Zámbó, B., Tabet, R., Riet, F., Dembélé, D., Mandel, J., Hocquemiller, M., Laufer, R., Piguet, F., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202114649 · Cited by 20 · see citing works
Increasing our understanding of human cognition through the study of fragile X syndrome
Cook, D., Nuro, E., & Murai, K. K. (2013) · Developmental Neurobiology · doi:10.1002/dneu.22096 · Cited by 20 · see citing works
A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity
Westmark, C. J. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00169 · Cited by 20 · see citing works
Self-citation
Rescue of Fmr1 phenotypes with mGluR5 inhibitors: MRZ-8456 versus AFQ-056
Westmark, P. R., Dekundy, A., Gravius, A., Danysz, W., & Westmark, C. J. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.08.008 · Cited by 19 · see citing works
Self-citation
Analysis of peripheral amyloid precursor protein in Angelman Syndrome
Erickson, C. A., Wink, L. K., Bayon, B. L., Ray, B., Schaefer, T. L., Pedapati, E. V., & Lahiri, D. K. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37811 · Cited by 18 · see citing works
Self-citation
Molecular systems evaluation of oligomerogenic APPE693Q and fibrillogenic APPKM670/671NL/PSEN1Δexon9 mouse models identifies shared features with human Alzheimer’s brain molecular pathology
Readhead, B., Haure‐Mirande, J., Zhang, B., Haroutunian, V. H., Gandy, S., Schadt, E. E., Dudley, J. T., & Ehrlich, M. E. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.167 · Cited by 14 · see citing works
Molecular convergence between Down syndrome and fragile X syndrome identified using human pluripotent stem cell models
Susco, S. G., Ghosh, S. D., Mazzucato, P., Angelini, G., Beccard, A., Barrera, V., Berryer, M. H., Messana, A., Lam, D., Hazelbaker, D. Z., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111312 · Cited by 14 · see citing works
Of local translation control and lipid signaling in neurons
Moine, H., & Vitale, N. (2018) · Advances in Biological Regulation · doi:10.1016/j.jbior.2018.09.005 · Cited by 13 · see citing works
Acute stress enhances synaptic plasticity in male mice via a microbiota-dependent mechanism
Rosell‐Cardona, C., Collins, M., O’Riordan, K. J., Goodson, M. S., Kelley‐Loughnane, N., Cryan, J. F., & Clarke, G. A. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110434 · Cited by 12 · see citing works
Self-citation
Fragile X syndrome
Pietropaolo, S., & Subashi, E. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781107360556.014 · Cited by 12 · see citing works
Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly
Sokol, D. K., & Lahiri, D. K. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1201723 · Cited by 11 · see citing works
The quest for fragile X biomarkers
Westmark, C. J. (2014) · Molecular and Cellular Pediatrics · doi:10.1186/s40348-014-0001-3 · Cited by 11 · see citing works
Self-citation
The mGluR Theory of Fragile X: From Mice to Men
Stoppel, L. J., Osterweil, E. K., & Bear, M. F. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804461-2.00009-3 · Cited by 9 · see citing works
Testing Fmr1KO Phenotypes in Response to GSK3 Inhibitors: SB216763 versus AFC03127
Westmark, P. R., Garrone, B., Ombrato, R., Milanese, C., Giorgio, F. P. D., & Westmark, C. J. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.751307 · Cited by 9 · see citing works
Self-citation
Dendrites in Autism Spectrum Disorders
Martínez‐Cerdeño, V., Maezawa, I., & Jin, L. (2016) · Springer eBooks · doi:10.1007/978-4-431-56050-0_20 · Cited by 8 · see citing works
Developing BACE-1 inhibitors for FXS
Westmark, C. J., Berry‐Kravis, E., Ikonomidou, C., Yin, J. C. P., & Puglielli, L. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00077 · Cited by 8 · see citing works
Self-citation
MPTAC links alkylation damage signaling to sterol biosynthesis
Suganuma, T., & Workman, J. L. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102270 · Cited by 7 · see citing works
Peripheral Amyloid Precursor Protein Derivative Expression in Fragile X Syndrome
McLane, R. D., Schmitt, L., Pedapati, E. V., Shaffer, R. C., Dominick, K. C., Horn, P. S., Groß, C., & Erickson, C. A. (2019) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2019.00049 · Cited by 7 · see citing works
Use of biomarkers in the diagnosis of Alzheimer’s disease in adults with intellectual disability
McFeely, A., O’Connor, A., & Kennelly, S. (2024) · The Lancet Healthy Longevity · doi:10.1016/j.lanhl.2024.100639 · Cited by 6 · see citing works
Age-Dependent Dysregulation of APP in Neuronal and Skin Cells from Fragile X Individuals
Cencelli, G., Pacini, L., Luca, A. D., Messia, I., Gentile, A., Kang, Y., Nobile, V., Tabolacci, E., Jin, P., Farace, M. G., et al. (2023) · Cells · doi:10.3390/cells12050758 · Cited by 6 · see citing works
Commentary: Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis
Westmark, C. J. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00029 · Cited by 6 · see citing works
Self-citation
Toward an understanding of the role of the exposome on fragile X phenotypes
Westmark, C. J. (2023) · International review of neurobiology · doi:10.1016/bs.irn.2023.08.007 · Cited by 5 · see citing works
Self-citation
DJ-1-mediated repression of the RNA-binding protein FMRP is predicted to impact known Alzheimer's disease-related protein networks
Uneri, A., McArdle, C. J., Deng, Z., Barth, S. H., Keene, D., Craft, S., & Raab‐Graham, K. F. (2024) · Journal of Alzheimer s Disease · doi:10.1177/13872877241291175 · Cited by 5 · see citing works
Human Pluripotent Stem Cells in Modeling Human Disorders: the Case of Fragile X Syndrome
Vershkov, D., & Benvenisty, N. (2016) · Regenerative Medicine · doi:10.2217/rme-2016-0100 · Cited by 5 · see citing works
sAPPα Inhibits Neurite Outgrowth in Primary Mouse Neurons via GABA B Receptor Subunit 1a
Barber, D., Salinas-Salinas, C., Houmam, S., Shukla, K., & Rice, H. C. (2026) · eNeuro · doi:10.1523/eneuro.0345-25.2026 · Cited by 4 · see citing works
Modeling Fragile X Syndrome Using Human Pluripotent Stem Cells
Vershkov, D., Ben‐Hur, T., & Benvenisty, N. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804461-2.00006-8 · Cited by 4 · see citing works
Oxytocin, Compulsion and Epilepsy: Insights from a Complex Behavioral and Neuronal Networks AssociationPreprint
Marroni, S. S., Santos, V. R., Castro, O. W., Tejada, J., Santos, J., de Oliveira, J. A. D., & Garcia-Cairasco, N. (2019) · bioRxiv · doi:10.1101/638452 · Cited by 2 · see citing works
Contribution of astrocytic calcium signaling to auditory hypersensitivity in a mouse model of fragile X syndrome
Bergdolt, L., Anding, A., Alshaqi, O., Arbabi, Z., Douchey, M., Eldridge, E., Hoffman, K., Reid, A., Sapkota, K., Monaghan, D. T., et al. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107355 · Cited by 3 · see citing works
Drug Discovery for Targeted Pharmacotherapy of Fragile X Syndrome
Scharf, S., Gasparini, F., Spooren, W., & Lindemann, L. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804461-2.00018-4 · Cited by 1 · see citing works
Impaired spatial processing in a mouse model of fragile X syndrome
Ghilan, M., Bettio, L. E. B., Noonan, A., Brocardo, P. S., Gil‐Mohapel, J., & Christie, B. R. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.05.012 · Cited by 3 · see citing works
Beyond Moco Biosynthesis―Moonlighting Roles of MoaE and MOCS2
Suganuma, T. (2022) · Molecules · doi:10.3390/molecules27123733 · Cited by 3 · see citing works
Serum matrix metalloproteinase-9 (MMP9) and amyloid-beta protein precursor (APP) as potential biomarkers in children with Fragile-X syndrome: A cross sectional study
Bekheet, M., Mansour, L. A., Elkaffas, R. H., Kamel, M. A., & Elmonem, M. A. (2023) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2023.110659 · Cited by 2 · see citing works
Hot iron branding--not a reasonable requirement for international trade in live ruminants.
Whiting, T. L. (2005) · PubMed Central · Cited by 2 · see citing works

Reversal of Fragile X Phenotypes by Manipulation of AbPP/Ab Levels in Fmr1KO Mice
Westmark, C. J., Westmark, P. R., O’riordan, K. J., Ray, B. C., Hervey, C. M., Salamat, S., Abozeid, S. H., Stein, K. M., Stodola, L. A., Tranfaglia, M. R., et al. (2016)
Self-citation
Autism, Alzheimer disease, and fragile X
Sokol, D. K., Maloney, B., Long, J. M., Ray, B., & Lahiri, D. K. (2011) · Neurology · doi:10.1212/wnl.0b013e3182166dc7 · Cited by 141 · see citing works
Self-citation
Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model
Goebel‐Goody, S. M., Wilson‐Wallis, E. D., Royston, S., Tagliatela, S. M., Naegele, J. R., & Lombroso, P. J. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00781.x · Cited by 108 · see citing works
Reversal of Disease-Related Pathologies in the Fragile X Mouse Model by Selective Activation of GABA B Receptors with Arbaclofen
Henderson, C., Wijetunge, L., Kinoshita, M. N., Shumway, M., Hammond, R. S., Postma, F. R., Brynczka, C., Rush, R., Thomas, A., Paylor, R., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004218 · Cited by 249 · see citing works
Fragile X and APP: a Decade in Review, a Vision for the Future
Westmark, C. J. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1344-x · Cited by 31 · see citing works
Self-citation

Authors: Westmark, C. J., Westmark, P. R., O'Riordan, K. J., Ray, B. C., Hervey, C. M., Salamat, M. S., Abozeid, S. H., Stein, K. M., Stodola, L. A., Tranfaglia, M., Burger, C., Berry-Kravis, E. M., & Malter, J. S.
Affiliations: University of Wisconsin–Madison (US)
Rush University Medical Center (US)
Fraxa Research Foundation (US)
Corresponding author: Westmark, Cara J.
ORCID: Westmark, Cara J.
Malter, James S.
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2011-10-26
Volume: 6
Issue: 10
Pages: e26549
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0026549
PMC: PMC3202540
OpenAlex: W1966255973
Cited by: 110
References: 92
Citations by year: 2026: 3 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 13 · 2015: 16 · 2014: 13 · 2013: 11 · 2012: 8
FWCI: 6.38
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: FRAXA Research Foundation
Waisman Center (P30 HD03352, HD03352)
National Institutes of Health (HD033.52)
National Institute on Drug Abuse (R01DA026067)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD03352., P30HD003352)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: fragile X syndrome, FMRP, amyloid precursor protein, amyloid-beta, Fmr1 knockout mice, audiogenic seizures, anxiety, dendritic spines, metabotropic glutamate receptors, long-term depression, plasma biomarkers, intellectual disability, autism spectrum disorder, Alzheimer's disease
MeSH terms: Animals, Brain Chemistry, Female, Fragile X Syndrome, Male, Neurons, Peptide Fragments, Phenotype, Genetic Therapy, Down-Regulation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Receptors, Metabotropic Glutamate, Mice, Knockout, Dendritic Spines, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Reversal of Fragile X Phenotypes by Manipulation of AβPP/Aβ Levels in Fmr1KO Mice

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks