ArticleCell reports2018
Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease.
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Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 55 citations in OpenAlex.
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- Roles in physiology and disease of the inositol phosphatase synaptojanin 1.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- Discovery and Characterization of a Selective Inhibitor of Synaptojanin1 5‑Phosphatase Activity.ACS pharmacology & translational science · 2025Article
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- What Can We Learn About Alzheimer's Disease from People with Down Syndrome?Current topics in behavioral neurosciences · 2025Review
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Authors and funding
17 authors at 7 institutions in 5 countries.
Andre M MirandaTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's, PT Government Associate Laboratory, 4806-909 Braga/Guimarães, Portugal.
Mathieu HermanTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Rong ChengTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; G. H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA.
Eden NahmaniTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Geoffrey BarrettTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Elizabeta MicevskaTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Gaelle FontaineSorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR7225, ICM, 75013 Paris, France.
Marie-Claude PotierSorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR7225, ICM, 75013 Paris, France.
Elizabeth HeadSanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA; Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY 40506, USA.
Frederick A SchmittSanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA; Department of Neurology, University of Kentucky, Lexington, KY 40506, USA.
Ira T LottDepartment of Physiology, University of Kentucky, Lexington, KY 40506, USA; Department of Pediatrics and Neurology, School of Medicine, University of California, Irvine (UCI), Orange, CA 92668, USA.
Ivonne Z Jiménez-VelázquezDepartment of Internal Medicine, University of Puerto Rico School of Medicine, San Juan, PR, USA.
Stylianos E AntonarakisDepartment of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, 1211 Geneva, Switzerland.
Gilbert Di PaoloTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Joseph H LeeTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; G. H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA; Departments of Epidemiology and Neurology, Columbia University Medical Center, New York, NY 10032, USA.
S Abid HussainiTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Catherine MarquerTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: cm3244@cumc.columbia.edu.
Columbia University Irving Medical Center · USCentre National de la Recherche Scientifique · FRUniversity of Kentucky · USUniversity of California, Irvine · USUniversity of Geneva · CHUniversity of Minho · PTUniversity of Puerto Rico System · PR
Funding
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MUC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0MBiomarkers of Alzheimer's Disease in Adults with Down SyndromeU01AG051412 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LOTT, IRA T., SCHUPF, NICOLE · 2015 to 2019
$26.3MUniversity of Kentucky Alzheimer's Disease Core Center - Biomarker CoreP30AG028383 · NIA · UNIVERSITY OF KENTUCKY · PI SCHMITT, FREDERICK · 2006 to 2020
$23.3MGenetic Epidemiology of Alzheimer's Disease in HispanicsR37AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2004 to 2013
$10.8MAging of Frontal Structure and Function in Down Syndrome and DementiaR01HD064993 · NICHD · UNIVERSITY OF KENTUCKY · PI HEAD, ELIZABETH, SCHMITT, FREDERICK · 2009 to 2019
$5.1MGENETIC EPIDEMIOLOGY OF ALZHEIMERS DISEASE IN HISPANICSR01AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD · 1999 to 2003
$4.6MProtective genetic factors of Alzheimer disease in PSEN1 Mutation Carriers in Puerto RicoR01AG058918 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LEE, JOSEPH HYUNGWOO · 2018 to 2022
$4.3MGenetic Studies of Alzheimer's Disease in Caribbean HispanicsRF1AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2015 to 2018
$3.3MEntorhinal-hippocampal circuit dysfunction in AD miceR01AG050425 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HUSSAINI, S. ABID · 2015 to 2019
$2.5MPredicting Cognitive Decline in Adults with Down SyndromeR01HD065160 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI LOTT, IRA T. · 2009 to 2013
$2.3MGenetic Modifiers of Alzheimer Disease in PSEN1 Mutation Carriers in Puerto RicoR56AG051876 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LEE, JOSEPH HYUNGWOO, MAYEUX, RICHARD P · 2016 to 2016
$842kNIA NIH HHS P30 AG028383NIA NIH HHS P50 AG016573NIA NIH HHS R01 AG015473NIA NIH HHS R01 AG050425NIA NIH HHS R01 AG058918NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG051876NIA NIH HHS U01 AG051412NIA NIH HHS U24 AG021886NICHD NIH HHS R01 HD064993NICHD NIH HHS R01 HD065160
Abstract
The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD.
Indexed as
AgingAlzheimer DiseaseAnimalsCognition DisordersHaplotypesHippocampusMemory DisordersMice, Inbred C57BLMice, TransgenicMutant ProteinsNerve Tissue ProteinsPhosphoric Monoester HydrolasesPlace CellsPolymorphism, Single NucleotideSynapsesMutant ProteinsNerve Tissue ProteinsPhosphoric Monoester Hydrolasessynaptojaninhyperexcitabilityin vivo electrophysiologyLong-term memoryneurodegenerative disorderssingle nucleotide polymorphismssynaptic dysfunctionSYNJ1
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