Cited by 562Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record.

Loss of the Presynaptic Vesicle Protein Synaptophysin in Hippocampus Correlates with Cognitive Decline in Alzheimer Disease

Open access

SZE, CHUN-I, TRONCOSO, JUAN C., KAWAS, CLAUDIA, MOUTION, PETER, PRICE, DONALD L., MARTIN, LEE J.·1997·Journal of Neuropathology and Experimental Neurology

DOI 10.1097/00005072-199708000-00011

Open this paper in CoChat — free account

Abstract

We tested the hypothesis that synaptic defects in the hippocampus of individuals with Alzheimer disease (AD) correlate with the severity of cognitive impairment. Three postmortem groups were studied: controls with normal and stable cognition; cognitively intact subjects with senile plaque densities diagnostic for possible AD (p-AD) and neurofibrillary changes characteristic of early AD (Braak stage III); and individuals with definite AD and neurofibrillary changes typical of incipient to severe AD (Braak stage III, V, or VI). Synaptophysin (a presynaptic vesicle protein) levels were quantified by immunoblotting of synaptic membrane fractions isolated from hippocampus, entorhinal cortex, caudate nucleus, and occipital cortex. Average synaptophysin levels were reduced in hippocampus when comparing definite AD to controls (55%, p < 0.0001), p-AD to control (25%, p < 0.005), and definite AD to p-AD (30%, p < 0.05), but levels in entorhinal cortex, occipital cortex, and caudate nucleus were either unchanged or less significantly altered than in hippocampus. By univariate analysis, hippocampal synaptophysin levels correlated with neuropsychological measurements, including Mini-mental state examination scores (r = 0.83, p < 0.0001) and Blessed scores (r = 0.74, P < 0.001), and with senile plaque densities (r = 0.89, p < 0.0001). We conclude that synaptic abnormalities in the hippocampus correlate with the severity of neuropathology and memory deficit in individuals with AD, and that this defect may predate neuropsychological evidence for cognitive impairment early in AD.

Integrity signals

Registry

Crossref · 10.1097/00005072-199708000-00011

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Sorted by citations

Items 301–400 of 562

Cyclin-dependent kinase 5, Munc18a and Munc18-interacting protein 1/X11α protein up-regulation in Alzheimer’s disease
Jacobs, E. H., Williams, R. J., & Francis, P. T. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.11.017 · Cited by 31
Effects of triptolide on the synaptophysin expression of hippocampal neurons in the AD cellular model
Nie, J., Zhou, M., Lu, C. B., Hu, X., Wan, B., Yang, B., & Li, Y. (2012) · International Immunopharmacology · doi:10.1016/j.intimp.2012.03.021 · Cited by 32
Computational discovery and experimental verification of tyrosine kinase inhibitor pazopanib for the reversal of memory and cognitive deficits in rat model neurodegeneration
Yang, Y., Li, G., Zhao, D., Yu, H., Zheng, X., Peng, X., Zhang, X., Fu, T., Hu, X., Niu, M., et al. (2015) · Chemical Science · doi:10.1039/c4sc03416c · Cited by 33
“27,28 We observed a decrease in the SYP level in the CA1 region of the model group compared to the control group by western blotting, whereas SYP expression level was increased in donepezil-and pazopanib-treated model rats (Fig.”
APOE-Sensitive Cholinergic Sprouting Compensates for Hippocampal Dysfunctions Due to Reduced Entorhinal Input
Bott, J.-B., Héraud, C., Cosquer, B., Herbeaux, K., Aubert, J., Sartori, M., Goutagny, R., & Mathis, C. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1174-16.2016 · Cited by 34
“The consecutive loss of glutamatergic inputs to the hippocampus (Hyman al., 1984, 1986) is the best correlate for memory impairment onset and progression to dementia (Sze et al., 1997; Scheff et al., 2006).”
Background
T-817MA, a neuroprotective agent, attenuates the motor and cognitive impairments associated with neuronal degeneration in P301L tau transgenic mice
Fukushima, T., Nakamura, A., Iwakami, N., Nakada, Y., Hattori, H., Hoki, S., Yamaguchi, H., Nakagawa, M., Terashima, N., & Narita, H. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.03.091 · Cited by 31
Uncovering Neurodegenerative Protein Modifications via Proteomic Profiling
Gallart‐Palau, X., Serra, A., & Sze, S. K. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.06.002 · Cited by 29
Lasting changes induced by mild alcohol exposure during embryonic development in BDNF , NCAM and synaptophysin‐positive neurons quantified in adult zebrafish
Mahabir, S., Chatterjee, D., Misquitta, K. A., Chatterjee, D., & Gerlai, R. T. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13975 · Cited by 31
“Synaptophysin also plays a vital role in learning and memory (Frick & Fernandez, 2003; Sze et al., 1997).”
Background
Mass synaptometry: High-dimensional multi parametric assay for single synapses
Gajera, C. R., Fernandez, R., Postupna, N. O., Montine, K. S., Fox, E. J., Tebaykin, D., Angelo, M., Bendall, S. C., Keene, C. D., & Montine, T. J. (2018) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2018.11.008 · Cited by 32
“Synaptic alterations, especially presynaptic changes, are cardinal feature of neurodegenerative diseases, including LBD, and AD, and strongly correlate with cognitive decline (DeKosky and Scheff, 1990; Dickson et al., 1995; Masliah et al., 1991; Scheff and Price, 2003; Sze et al., 1997; Terry, 1996; Terry et al., 1991…”
Background
Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer’s Disease
Petukhova, E. O., Mukhamedshina, Y. O., Salafutdinov, I. I., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190150 · Cited by 31
Green tea extract containing enhanced levels of epimerized catechins attenuates scopolamine-induced memory impairment in mice
Bae, H. J., Kim, J., Jeon, S. J., Kim, J., Goo, N., Jeong, Y., Cho, K., Cai, M., Jung, S. Y., Kwon, K. J., et al. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.112923 · Cited by 32
Increased Levels of Extracellular Microvesicle Markers and Decreased Levels of Endocytic/Exocytic Proteins in the Alzheimer’s Disease Brain
Musunuri, S., Khoonsari, P. E., Mikus, M. S., Wetterhall, M., Månberg, A., Lannfelt, L., Erlandsson, A., Bergquist, J., Ingelsson, M., Shevchenko, G., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160271 · Cited by 34
“Furthermore, several studies have shown that the loss of presynaptic vesicle proteins is associated with AD pathogenesis by contributing to the learning impairment and cognitive deﬁcits [10, 11].”
Crocin attenuates the granular cells damages on the dentate gyrus and pyramidal neurons in the CA3 regions of the hippocampus and frontal cortex in the rat model of Alzheimer's disease
Hadipour, M., Meftahi, G. H., Afarinesh, M. R., Jahromi, G. P., & Hatef, B. (2020) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2020.101837 · Cited by 31
Transgenic Mouse Models of Alzheimer's Disease and Amyotrophic Lateral Sclerosis
Borchelt, D., Wong, P. C., Sisodia, S. S., & Price, D. L. (1998) · Brain Pathology · doi:10.1111/j.1750-3639.1998.tb00198.x · Cited by 29
“These types of cellular abnormalities involving neural circuits have profound clinical consequences presumed to be the result of compromised synaptic interactions in affected regions of the brain (53, 59, 88, 158, 159, 161, 162, 191, 223, 248, 251).”
Self-citation
α-Synuclein-Induced Synapse Damage in Cultured Neurons Is Mediated by Cholesterol-Sensitive Activation of Cytoplasmic Phospholipase A2
Bate, C., & Williams, A. (2015) · Biomolecules · doi:10.3390/biom5010178 · Cited by 28
“The loss of synaptic proteins including synaptophysin shows a close correlation with cognitive decline in Alzheimer’s disease [17,18] and reflects the loss of other synaptic proteins from neuronal cultures [19].”
Background
Altered expression and localization of synaptophysin in developing cerebellar cortex of neonatal rats due to maternal diabetes mellitus
Hami, J., Vafaei‐Nezhad, S., Ivar, G., Sadeghi, A., Ghaemi, K., Mostafavizadeh, M., & Hosseini, M. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9864-4 · Cited by 26
Dysfunctional proteins in neuropsychiatric disorders: From neurodegeneration to autism spectrum disorders
Jęśko, H. M., Cieślik, M., Gromadzka, G., & Adamczyk, A. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104853 · Cited by 30
Age-Related Transcriptional Deregulation of Genes Coding Synaptic Proteins in Alzheimer's Disease Murine Model: Potential Neuroprotective Effect of Fingolimod
Jęśko, H. M., Wieczorek, I., Wencel, P. L., Gąssowska-Dobrowolska, M., Lukiw, W. J., & Strosznajder, R. P. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.660104 · Cited by 25
“Reduced SYP also correlates with AD severity (Sze et al., 1997; Heffernan et al., 1998).”
Background
Serine racemase: a key player in apoptosis and necrosis
Canu, N., Ciotti, M. T., & Pollegioni, L. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00009 · Cited by 29
Pregnancy and lactation differentially modify the transcriptional regulation of steroidogenic enzymes through DNA methylation mechanisms in the hippocampus of aged rats
Rossetti, M. F., Varayoud, J., Lazzarino, G. P., Luque, E. H., & Ramos, J. G. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.03.037 · Cited by 28
“Moreover, the modification of BDNF and 443 syp levels have been described during normal aging and AD and this fact was correlated with cognitive 444 decline and other neuronal dysfunctions (Heinonen et al., 1995; Liu et al., 2005; Sze et al., 1997; Tapia-445 Arancibia et al., 2008).”
Background
Differential changes in synaptic terminal protein expression between nucleus accumbens core and shell in the amphetamine-sensitized rat
Subramaniam, S., Marcotte, E. R., & Srivastava, L. K. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02347-2 · Cited by 28
Circulating small extracellular vesicles in Alzheimer’s disease: a case–control study of neuro-inflammation and synaptic dysfunction
Singh, R., Rai, S., Bharti, P. S., Zehra, S., Gorai, P. K., Modi, G. P., Rani, N., Dev, K., Inampudi, K. K., Y., V. V., et al. (2024) · BMC Medicine · doi:10.1186/s12916-024-03475-z · Cited by 28
“This suggests synaptic degeneration, which has also been discussed in several studies [59, 63, 64].”
BackgroundResult
N-Acetylcysteine Amide against Aβ-Induced Alzheimer’s-like Pathology in Rats
Alkandari, A. F., Madhyastha, S., & Rao, M. S. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612733 · Cited by 27
“Both prophylactic and restorative treatments of NACA elevated DCX protein levels in the hippocampus and DCX-positive neurons in the dentate gyrus, indicating enhanced neuronal proliferation.”
Thy1-ApoE4/C/EBPβ double transgenic mice act as a sporadic model with Alzheimer’s disease
Qian, Z., Wang, Z., Li, B., Meng, X., Kuang, Z., Li, Y., Yang, Y., & Ye, K. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02565-x · Cited by 28
The effect of IL-1β on synaptophysin expression and electrophysiology of hippocampal neurons through the PI3K/Akt/mTOR signaling pathway in a rat model of mesial temporal lobe epilepsy
Xiao, Z., Peng, J., Wu, L., Arafat, A., & Yin, F. (2017) · Neurological Research · doi:10.1080/01616412.2017.1312070 · Cited by 28
Proteomic studies of cerebrospinal fluid biomarkers of Alzheimer’s disease: an update
Portelius, E., Brinkmalm, G., Pannee, J., Zetterberg, H., Blennow, K., Dahlén, R., Brinkmalm, A., & Gobom, J. (2017) · Expert Review of Proteomics · doi:10.1080/14789450.2017.1384697 · Cited by 26
The effect of olanzapine on spatial memory impairment, depressive-like behavior, pain perception, and BDNF and synaptophysin expression following childhood chronic unpredictable mild stress in adult male and female rats
Farahani, Z., Vaseghi, S., Rajabbeigi, E., & Yekta, B. G. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115039 · Cited by 28
Selective distribution and dynamic modulation of miRNAs in the synapse and its possible role in Alzheimer's Disease
Garza-Manero, S., Pichardo‐Casas, I., Arias, C., Vaca, L. A., & Zepeda, A. (2013) · Brain Research · doi:10.1016/j.brainres.2013.12.009 · Cited by 28
Effects of Curcumin and Boric Acid Against Neurodegenerative Damage Induced by Amyloid Beta (1-42)
Hacıoğlu, C., Kar, F., Kar, E., Kara, Y., & Kanbak, G. (2020) · Biological Trace Element Research · doi:10.1007/s12011-020-02511-2 · Cited by 27
Heterophyllin B, a cyclopeptide from Pseudostellaria heterophylla, enhances cognitive function via neurite outgrowth and synaptic plasticity
Yang, Z., Zhang, C., Li, X., Ma, Z., Ge, Y., Qian, Z., & Song, C. (2021) · Phytotherapy Research · doi:10.1002/ptr.7212 · Cited by 26
“The expression of SYP and PSD-95 decreases with aging and progression of Alzheimer's disease, leads to a decline in cognitive function (Savioz, Leuba, & Vallet, 2014; Sze et al., 1997).”
Background
Functional tolerance to mechanical deformation developed from organotypic hippocampal slice cultures
Kang, W. H., & Morrison, B. (2014) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-014-0622-4 · Cited by 25
A unifying hypothesis of Alzheimer's disease. II. Pathophysiological processes
Heininger, K. (1999) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/(sici)1099-1077(199912)14:8 · Cited by 27
Age-Related Mitochondrial Alterations without Neuronal Loss in the Hippocampus of a Transgenic Model of Alzheimer's Disease
Cuadrado‐Tejedor, M., Cabodevilla, J. F., Zamarbide, M., et al. (2013) · Current Alzheimer Research · doi:10.2174/1567205011310040005 · Cited by 25
Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer’s disease
Dong, X., Gao, W., KONG, W.-N., XIE, H.-L., PENG, Y., Shao, T.-M., Yu, W., & Xi-qing, C. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2234 · Cited by 26
“Furthermore, synaptic dysfunction has been identified in the associated cortices and hippocampus of the AD brain (41,42).”
Entorhinal verrucae geometry is coincident and correlates with Alzheimer’s lesions: a combined neuropathology and high-resolution ex vivo MRI analysis
Augustinack, J. C., Huber, K. E., Postelnicu, G. M., Kakunoori, S., Wang, R., van der Kouwe, A. J. W., Wald, L. L., Stein, T. D., Frosch, M. P., & Fischl, B. R. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0929-5 · Cited by 25
“, synaptophysin) [11, 24, 45] in hippocampus and entorhinal cortex in AD, notably early in disease progression.”
Background
Fusion of ULS Group Constrained High- and Low-Order Sparse Functional Connectivity Networks for MCI Classification
Li, Y., Liu, J., Peng, Z., Sheng, C., Kim, M., Yap, P., Chong-yaw Wee, A., & Shen, D. G. (2019) · Neuroinformatics · doi:10.1007/s12021-019-09418-x · Cited by 26
Subcutaneous Administration of AMD3100 into Mice Models of Alzheimer’s Disease Ameliorated Cognitive Impairment, Reduced Neuroinflammation, and Improved Pathophysiological Markers
Gavriel, Y., Rabinovich-Nikitin, I., Ezra, A., Barbiro, B., & Solomon, B. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200506 · Cited by 27
“Loss of the presynaptic vesicle protein synaptophysin in the hippocampus correlates with cognitive decline in AD [52].”
Increased Tau Phosphorylation and Tau Truncation, and Decreased Synaptophysin Levels in Mutant BRI2/Tau Transgenic Mice
Garringer, H. J., Murrell, J. R., Sammeta, N., Gnezda, A., Ghetti, B. F., & Vidal, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056426 · Cited by 24
“Early loss of synaptic contacts has been associated with the initiation of cognitive decline, followed by neuritic damage, and neuronal cell loss [53], with loss of hippocampal synaptophysin correlating with cognitive decline in AD [34].”
Background
Intraneuronal Aβ Accumulation, Amyloid Plaques, and Synapse Pathology in Alzheimer’s Disease
Capetillo‐Zarate, E., Gracia, L., Tampellini, D., & Gouras, G. K. (2012) · Neurodegenerative Diseases · doi:10.1159/000334762 · Cited by 25
Significance of Molecular Signaling for Protein Translation Control in Neurodegenerative Diseases
Chang, R. C., Yu, M.-S., & Lai, C. S.-W. (2006) · Neurosignals · doi:10.1159/000102599 · Cited by 22
St. John's wort may relieve negative effects of stress on spatial working memory by changing synaptic plasticity
Trofimiuk, E., Hołownia, A., & Braszko, J. J. (2011) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-011-0604-3 · Cited by 23
“In patients with Alzheimer's disease, SYP immunoreactivity is significantly reduced in the hippocampus and frontal cortex and is associated with impaired cognitive functions (Sze et al. 1997).”
Background
N-acetylcysteine treatment attenuates the cognitive impairment and synaptic plasticity loss induced by streptozotocin
Costa, M. D., Bernardi, J., Costa, L., Fiuza, T. D. L., Brandão, R., Ribeiro, M. F., Amaral, J. D., Rodrigues, C. M. P., & Pereira, M. E. (2017) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2017.05.008 · Cited by 23
Cyclosporine A (CsA) prevents synaptic impairment caused by truncated tau by caspase-3
Tapia-Monsalves, C., Olesen, M. A., Villavicencio-Tejo, F., & Quintanilla, R. A. (2023) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2023.103861 · Cited by 24
A Ketogenic Diet may Improve Cognitive Function in Rats with Temporal Lobe Epilepsy by Regulating Endoplasmic Reticulum Stress and Synaptic Plasticity
Qiao, Q., Tian, S., Zhang, Y., Che, L., Li, Q., Qu, Z., & Wang, W. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03659-3 · Cited by 22
“…atory glutamate synaptic PSD, and Syp, Syt1 and SNAP-25 are involved in the release of endogenous glutamate, the endocytosis and exocytosis of synaptic vesicles and the growth of dendrites and axons, respectively, all of which play important roles in the induction and maintenance of LTP [53 – 55].”
Exendin-4 Prevents Memory Loss and Neuronal Death in Rats with Sporadic Alzheimer-Like Disease
Zago, A. M., Carvalho, F. B., Rahmeier, F. L., Santin, M., Guimarães, G. R., Gutierres, J. M., & Fernandes, M. D. C. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03698-w · Cited by 23
“For example, in patients with Alzheimer’s disease, synaptophysin immunoreactivity is significantly reduced in the frontal cortex and hippocampus, and this reduction is correlated with impaired cognitive abilities [73].”
cAMP-Inhibits Cytoplasmic Phospholipase A2 and Protects Neurons against Amyloid-β-Induced Synapse Damage
Bate, C., & Williams, A. (2015) · Biology · doi:10.3390/biology4030591 · Cited by 22
“The progressive dementia associated with AD is thought to be due to synaptic failure [2] and a reduction in synaptic proteins correlates strongly with cognitive decline [3,4].”
Background
Cerebrospinal fluid neurogranin in an inducible mouse model of neurodegeneration: A translatable marker of synaptic degeneration
Höglund, K., Schussler, N., Kvartsberg, H., Smailović, U., Brinkmalm, G., Liman, V., Becker, B., Zetterberg, H., Cedazo-Mı́nguez, Á., Janelidze, S., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104645 · Cited by 22
Antiamnesic effects of tofisopam against scopolamine-induced cognitive impairments in rats
Üçel, U. İ., Can, Ö. D., Özkay, Ü. D., & Ulupınar, E. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2020.172858 · Cited by 22
Ferroptosis and cognitive impairment: Unraveling the link and potential therapeutic targets
Naderi, S., Khodagholi, F., Janahmadi, M., Motamedi, F., Torabi, A., Batool, Z., Heydarabadi, M. F., & Pourbadie, H. G. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110210 · Cited by 23
Amyloid pathology and synaptic loss in pathological aging
Gkanatsiou, E., Nilsson, J., Toomey, C. E., Vrillon, A., Kvartsberg, H., Portelius, E., Zetterberg, H., Blennow, K., Brinkmalm, A., Lashley, T., et al. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15487 · Cited by 23
“In post- mortem brain tissue, its level has been found to be reduced in AD (Davidsson & Blennow, 1998; Sze et al., 1997), and studies indicate a more severe loss than for other synaptic proteins including synaptotagmin- 1 (Reddy et al., 2005).”
Background
Neurophysiological consequences of synapse loss in progressive supranuclear palsy
Adams, N. E., Jafarian, A., Perry, A., Rouse, M. A., Shaw, A. D., Murley, A. G., Cope, T. E., Bevan-Jones, W. R., Passamonti, L., Street, D., et al. (2023) · Brain · doi:10.1093/brain/awac471 · Cited by 21
“For example, in Alzheimer’s disease, 6,38 PSP 10 and frontotemporal dementia 12 synaptic density correlates with cognitive function.”
Inhibition of nitric oxide synthase increases synaptophysin mRNA expression in the hippocampal formation of rats
Joca, S. R. L., Guimarães, F. S., & Del-Bel, E. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.05.026 · Cited by 21
Ameliorative effects of a non-competitive BACE1 inhibitor TAK-070 on Aβ peptide levels and impaired learning behavior in aged rats
Takahashi, H., Fukumoto, H., Maeda, R., Terauchi, J., Kato, K., & Miyamoto, M. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.032 · Cited by 21
Glutamatergic Neurotransmission Expression Profiling in the Mouse Hippocampus After Perforant-Path Transection
Ginsberg, S. D. (2005) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200512000-00004 · Cited by 22
Locating the neuronal targets for caffeine
Fredholm, B. B., Arslan, G., Kull, B., & Svenningsson, P. (1998) · Drug Development Research · doi:10.1002/(sici)1098-2299(199811/12)45:3/4 · Cited by 5
Comparison of gene expression in old versus young rat hippocampus by cDNA array
Cho, K. S., Choi, J., Ha, C. M., Son, Y. J., Choi, W. S., & Lee, B. J. (2002) · Neuroreport · doi:10.1097/00001756-200203040-00008 · Cited by 21
Submicromolar Aβ42 reduces hippocampal glutamate receptors and presynaptic markers in an aggregation-dependent manner
Wisniewski, M. L., Hwang, J., & Bahr, B. A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.09.011 · Cited by 20
Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking
Sohn, Y. I., Lee, N. J., Chung, A., Saavedra, J. M., Turner, R. S., Pak, D. T. S., & Hoe, H. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.08.091 · Cited by 20
“We measured the puncta number of synaptophysin and PSD-95 because it is well known that PSD-95 is involved in dendritic spine formation at the postsynaptic junction [21] and that synaptophysin is a presynaptic marker related to cognitive function [22].”
Imbalance in the response of pre- and post-synaptic components to amyloidopathy
Stephen, T., Tamagnini, F., Piegsa, J., Sung, K., Harvey, J., Oliver‐Evans, A., Murray, T. K., Ahmed, Z., Hutton, M. L., Randall, A. D., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50781-1 · Cited by 23
Genotype Load Modulates Amyloid Burden and Anxiety-Like Patterns in Male 3xTg-AD Survivors despite Similar Neuro-Immunoendocrine, Synaptic and Cognitive Impairments
Muntsant-Soria, A., & Giménez‐Llort, L. (2021) · Biomedicines · doi:10.3390/biomedicines9070715 · Cited by 21
“tophysin expression in Alzheimer’s patient’s brain areas [61,62].”
Background
Inhibition of mGluR5/PI3K-AKT Pathway Alleviates Alzheimer’s Disease-Like Pathology Through the Activation of Autophagy in 5XFAD Mice
Chen, Y., Zhang, Y., Chen, Q., Liu, Y., Wei, X., Wu, M., Zhang, K., Liu, Y., & Wei, W. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-221058 · Cited by 19
“Synaptic defects are characteristics of AD pathology and are directly related to cognitive function [13].”
Dietary High-Fat Promotes Cognitive Impairment by Suppressing Mitophagy
Wen, J., Wang, Y., Wang, C., Yuan, M., Chen, F., Zou, Q., Cai, Z., & Zhao, B. (2023) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2023/4822767 · Cited by 20
“Synaptic pathology in AD initiates at the presynaptic terminal and diffuses to postsynaptic sites [36], and Tau acts aberrantly during synaptic decline.”
Background
Adult-onset deactivation of autophagy leads to loss of synapse homeostasis and cognitive impairment, with implications for alzheimer disease
Jasutkar, H. G., Wasserlein, E. M., Ishola, A. O., Litt, N. A., Staniszewski, A., Arancio, O., & Yamamoto, A. (2024) · Autophagy · doi:10.1080/15548627.2024.2368335 · Cited by 20
Large‐scale N‐glycoproteome map of rat brain tissue: Simultaneous characterization of insoluble and soluble protein fractions
Qiao, X., Tao, D., Qu, Y., et al. (2011) · PROTEOMICS · doi:10.1002/pmic.201000715 · Cited by 19
“To date, some glycoproteins in brain have been reported to be closely related to various diseases, such as P-glycoprotein with AIDS and brain tumor [24, 25]; synaptophysin with epilepsy and Alzheimer’s disease [26, 27].”
Background
A combination extract of ginseng, epimedium, polygala, and tuber curcumae increases synaptophysin expression in APPV717I transgenic mice
Shi, J., Tian, J., Zhang, X., Wei, M., Yin, L. W., Wang, P., & Wang, Y. (2012) · Chinese Medicine · doi:10.1186/1749-8546-7-13 · Cited by 19
“Although Aβ accumulation in neurons plays an important role in AD pathogenesis [3,4], changes in the density of presynaptic markers, specifically synaptophysin (SYP), were suggested to be better correlated with disease progression and cognitive decline [5-9].”
Background
3-Hydroxy-3-Methylglutaric Acid Impairs Redox and Energy Homeostasis, Mitochondrial Dynamics, and Endoplasmic Reticulum–Mitochondria Crosstalk in Rat Brain
da Rosa, M. S., da Rosa‐Junior, N. T., Parmeggiani, B., et al. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00122-x · Cited by 19
Investigating the Effect of Inosine on Brain Purinergic Receptors and Neurotrophic and Neuroinflammatory Parameters in an Experimental Model of Alzheimer’s Disease
Teixeira, F. C., Soares, M. S. P., Blödorn, E. B., Domingues, W. B., Reichert, K. P., Zago, A. M., Carvalho, F. B., Gutierres, J. M., Gonçales, R. A., Fernandes, M. D. C., et al. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02627-z · Cited by 19
Electrically evoked local muscle contractions cause an increase in hippocampal BDNF
Maekawa, T., Ogasawara, R., Tsutaki, A., Lee, K., Nakada, S., Nakazato, K., & Ishii, N. (2018) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2017-0536 · Cited by 22
c-Abl Deficiency Provides Synaptic Resiliency Against Aβ-Oligomers
Gutiérrez, D. A., Vargas, L. M., Chandía-Cristi, A., de la Fuente, C., Leal, N. R., & Alvarez, A. R. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00526 · Cited by 19
“In AD mice models and AD patients, AβOs induce synapse loss, decreasing levels of pre- and post-synaptic proteins and reducing the number of synaptic contacts (Sze et al., 1997; Masliah et al., 2001; Reddy et al., 2005; Calabrese et al., 2007).”
Background
Amyloid-β expression in retrosplenial cortex of triple transgenic mice: relationship to cholinergic axonal afferents from medial septum
Robertson, R. T., Baratta, J. L., Yu, J., & LaFerla, F. M. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.09.024 · Cited by 16
Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease
Barranco, N., Plá, V., Alcolea, D. A., Sánchez-Domínguez, I., Fischer‐Colbrie, R., Ferrer, I., Lleó, A., & Aguado, F. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00263-0 · Cited by 15
“In contrast to the global loss of major SV components (e.g. Syp and Rab3A) [53, 54], we show that the total levels of DCV proteins remain mostly invariable in the cerebral cortex of AD patients.”
Background
Analysis of the Time-Dependent Changes of Phospholipids in the Brain Regions of a Mouse Model of Alzheimer's Disease
Haque, M. A., Omori, N., Sheikh, A. M., Yano, S., Osago, H., Mitaki, S., Azad, A. K., Sakai, H., Michikawa, M., & Nagai, A. (2022) · Brain Research · doi:10.1016/j.brainres.2022.148197 · Cited by 17
Transcriptional signatures of hippocampal tau pathology in primary age-related tauopathy and Alzheimer’s disease
Stein-O’Brien, G., Palaganas, R. G., Meyer, E. M., Redding‐Ochoa, J., Pletniková, O., Guo, H., Bell, W. R., Troncoso, J. C., Huganir, R. L., & Morris, M. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115422 · Cited by 18
“While there is evidence of synaptic loss in the hippocampus in both PART and AD, the overall pattern of synaptic changes may be distinct[16, 19-21].”
Self-citation
LMDS-1, a potential TrkB receptor agonist provides a safe and neurotrophic effect for early-phase Alzheimer’s disease
Fan, C.-H., Lin, C.-W., Huang, H.-J., Lee‐Chen, G., Sun, Y., Lin, W., Chen, C., Chang, K., Su, M., & Hsieh‐Li, H. M. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05602-z · Cited by 17
The oxidatively damaged DNA and amyloid-β oligomer hypothesis of Alzheimer's disease
Sanders, O. D., Rajagopal, L., & Rajagopal, J. A. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.08.019 · Cited by 18
Chronic elevation of amyloid precursor protein in the neocortex or hippocampus of marmosets with selective cholinergic lesions
Ramírez, M. J., Ridley, R. M., Maclean, C. J., Honer, W. G., Francis, P. T., & Baker, H. F. (2001) · Journal of Neural Transmission · doi:10.1007/s007020170031 · Cited by 17
“These presynaptic terminal proteins are altered in amount and in distribution in a variety of human neurodegenerative conditions, including AD, and are considered to relate to the cognitive impairment (Goto and Hirano, 1990; Honer et al., 1992; Sze et al., 1997; Wakabayashi et al., 1994).”
Neuronal Differentiation Is Accompanied by Increased Levels of SNAP‐25 Protein in Fetal Rat Primary Cortical Neurons
Bailey, J. A., & Lahiri, D. K. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1377.001 · Cited by 17
Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer’s disease mice
Huang, H., Ai, W.-Q., Wei, N., Zhu, L., Liu, Z., Zhou, C.-W., Deng, M., Zhang, W.-T., Zhang, J.-C., Yang, C., et al. (2023) · Protein & Cell · doi:10.1093/procel/pwad056 · Cited by 17
“Numerous studies have reported that loss of synaptic contacts in both the neocortex and the hippocampus is one of the key neuropathological findings in socially isolated (SI) individuals (Mumtaz et al., 2018), as well as in AD patients (Ferrero et al., 2018; Sze et al., 1997).”
Background
Aging-dependent loss of functional connectivity in a mouse model of Alzheimer’s disease and reversal by mGluR5 modulator
Mandino, F., Shen, X., Desrosiers-Grégoire, G., O’Connor, D. A., Mukherjee, B., Owens, A., Qu, A., Onofrey, J. A., Papademetris, X., Chakravarty, M. M., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02779-z · Cited by 19
Elevation of BACE in an Aβ rat model of Alzheimer's disease: exacerbation by chronic stress and prevention by nicotine
Alkadhi, K. A., Alzoubi, K. H., Srivareerat, M., & Tran, T. T. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000162 · Cited by 16
“2002) of pre-synaptic terminals in neocortical and hippocampal regions (Sze et al. 1997; Terry et al. 1991), which are correlated with progressive cognitive decline.”
Background
Faster kinetics of quantal catecholamine release in mouse chromaffin cells stimulated with acetylcholine, compared with other secretagogues
Calvo‐Gallardo, E., López‐Gil, Á., Méndez‐López, I., Martínez‐Ramírez, C., Padín, J. F., & Garcı́a, A. G. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13849 · Cited by 16
TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition
Franco, M. L., García-Carpio, I., Comaposada-Baró, R., Escribano-Saiz, J. J., Chávez‐Gutiérrez, L., & Vilar, M. (2021) · Life Science Alliance · doi:10.26508/lsa.202000844 · Cited by 12
“Of relevance, cholinergic neurons are one of the few populations of the CNS that express relatively high levels of p75 NTR during adulthood and their severe lost during AD correlates with changes in hippocampal synaptic transmission and progression of dementia (Sze et al, 1997).”
Cryptotanshinone Attenuates Amyloid-β42-induced Tau Phosphorylation by Regulating PI3K/Akt/GSK3β Pathway in HT22 Cells
Lyu, D., & Jia, J. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02850-2 · Cited by 16
miR-128 as a Regulator of Synaptic Properties in 5xFAD Mice Hippocampal Neurons
Shvarts-Serebro, I., Sheinin, A., Gottfried, I., Adler, L., Schottlender, N., Ashery, U., & Barak, B. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01862-2 · Cited by 15
Enriched Environment Decreases Cognitive Impairment in Elderly Rats With Prenatal Mobile Phone Exposure
Hong, S., Huang, H., Yang, M., Wu, H., & Wang, L. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00162 · Cited by 15
The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer’s disease
Cade, S., Zhou, X., & Bobrovskaya, L. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2021-0111 · Cited by 14
“Reductions in synaptic proteins, dendritic spine density and synapse loss are well establishedpathologies in post-mortemADbrains (Mi et al. 2017; Proctor et al. 2010; Scheff et al. 2007; Sze et al. 1997).”
Background
Neuronal MHC-I complex is destabilized by amyloid-β and its implications in Alzheimer’s disease
Kim, M.-S., Cho, K., Cho, M.-H., Kim, N., Kim, K., Kim, D., & Yoon, S. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01132-1 · Cited by 14
“2A, D), indicating synaptic degeneration in AD brains [28, 29].”
Background
Lecanemab blocks the effects of the Aβ/fibrinogen complex on blood clots and synapse toxicity in organotypic culture
Singh, P. K., Pires, E. N. S., Chen, Z., Torrente, D., Calvano, M., Sharma, A., Strickland, S., & Norris, E. H. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2314450121 · Cited by 16
Amyloid-β (1-42) peptide induces rapid NMDA receptor-dependent alterations at glutamatergic synapses in the entorhinal cortex
Olajide, O. J., & Chapman, C. A. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.05.006 · Cited by 14
Green Tea Suppresses Amyloid β Levels and Alleviates Cognitive Impairment by Inhibiting APP Cleavage and Preventing Neurotoxicity in 5XFAD Mice
Kan, Z., Wang, Y., Chen, Q., Tang, X., Thompson, H. J., Huang, J., Zhang, J., Gao, F., Shen, Y., & Wan, X. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202100626 · Cited by 15
Intraneuronal accumulation of Aβ42 induces age-dependent slowing of neuronal transmission in Drosophila
Lin, J., Wang, W.-A., Zhang, X., Liu, H., Zhao, X., & Huang, F.-D. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1409-9 · Cited by 14
“with Alzheimer’s disease (AD) correlates with the degree of dementia([1-3]).”
Background
Glycine Administration Alters MAPK Signaling Pathways and Causes Neuronal Damage in Rat Brain: Putative Mechanisms Involved in the Neurological Dysfunction in Nonketotic Hyperglycinemia
Moura, A. P., Parmeggiani, B., Gasparotto, J., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0319-z · Cited by 14
Human LRRK2 G2019S mutation represses post-synaptic protein PSD95 and causes cognitive impairment in transgenic mice
Adeosun, S. O., Hou, X., Zheng, B., Melrose, H. L., Mosley, T. H., & Wang, J. M. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.05.001 · Cited by 14
“…(Migaud et al., 1998; Schmitt, Tanimoto, Seeliger, Schaeffel, & Leube, 2009) as well as in Alzheimer’s disease subjects (Counts, Nadeem, Lad, Wuu, & Mufson, 2006; Proctor, Coulson, & Dodd, 2010; Sze et al., 1997), we decided to assess the level of synaptic protein expression in their hippocampus.”
Genetically Engineered Models Relevant to Neurodegenerative Disorders: Their Value for Understanding Disease Mechanisms and Designing/Testing Experimental Therapeutics
Wong, P. C., Cai, H., Borcheit, D. R., & Price, D. L. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:2:233 · Cited by 14
“in target fields (Whitehouse et al., 1982; Francis et al., 1994; Sze et al., 1997; Price and Sisodia, 1998; Masliah, 1998); the disruption of synaptic communication in affected regions/circuits leads to memory/cognitive impairments and, finally, severe dementia (Morrison and Hof, 1997; Price and Sisodia, 1998).”
BackgroundSelf-citation
Extracellular Vesicle-Serpine-1 Affects Neural Progenitor Cell Mitochondrial Networks and Synaptic Density: Modulation by Amyloid Beta and HIV-1
Andras, I. E., Serrano, N., Djuraskovic, I., Fattakhov, N. S., Sun, E., & Toborek, M. J. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03456-y · Cited by 13
“Loss of synaptophysin was found in AD [73] and learning and memory deficits have been demonstrated in synaptophysin knockout mice [74].”
Ultrastructural analysis of hippocampal pyramidal neurons from apolipoprotein E-deficient mice treated with a cathepsin inhibitor
Díaz-Cintra, S. Y., Yong, A. P., Aguilar, A., et al. (2004) · Journal of Neurocytology · doi:10.1023/b:neur.0000029647.41374.98 · Cited by 13
“CHANGES IN AXOSOMATIC SYNAPSES The synaptic defects in the hippocampus of individuals with AD correlate with the severity of cognitive impairment (Sze et al., 1997).”
Background
Prenatal to early postnatal neurotrophic treatment prevents Alzheimer-like behavior and pathology in mice
Wei, W., Wang, Y., Liu, Y., Dai, C., Tung, Y. C., Liu, F., & Iqbal, K. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00666-7 · Cited by 13
Inhibition of PLK2 activity affects APP and tau pathology and improves synaptic content in a sex-dependent manner in a 3xTg mouse model of Alzheimer's disease
Martínez-Drudis, L., Sheta, R., Pellegrinato, R., Loukili, S., Tremblay, C., Calon, F., Rivest, S., & Oueslati, A. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105833 · Cited by 12
Vesicular Glutamate Transporter Changes in the Cortical Default Mode Network During the Clinical and Pathological Progression of Alzheimer’s Disease
Mi, Z., Abrahamson, E. E., Ryu, A. Y., Malek‐Ahmadi, M. H., Kofler, J., Fish, K. N., Sweet, R. A., Villemagne, V. L., Schneider, J. A., Mufson, E. J., et al. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221063 · Cited by 15
“Loss of synapses is a well-established biopathological correlate of impaired cognition and dementia in AD [12–17], while the relative contributions of amyloid and tau lesionstocognitiveimpairmentislessclear.”
Synaptogenesis in the cerebellum of offspring born to diabetic mothers
Hami, J., Vafaei‐Nezhad, S., Sadeghi, A., Ghaemi, K., Taheri, M. M. H., Fereidouni, M., Ivar, G., & Hosseini, M. (2017) · Journal of Pediatric Neurosciences · doi:10.4103/jpn.jpn_144_16 · Cited by 12
Neuroprotective Effects of Nicotine on Hippocampal Long-Term Potentiation in Brain Disorders
Alkadhi, K. A. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.247841 · Cited by 14
“…a marked loss of a7- and a4b2-nAChRs (Pettit et al., 2001; Auld et al., 2002; Lahiri et al., 2002; Utsuki et al., 2002; Mattson, 2004) and of presynaptic terminals in neocortical and hippocampal regions (Terry et al., 1991; Sze et al., 1997), which are correlated with progressive cognitive decline.”
Background

Authors: SZE, C.-I., TRONCOSO, J. C., KAWAS, C., MOUTION, P., PRICE, D. L., & MARTIN, L. J.
Affiliations: University of Colorado Health (US)
Johns Hopkins University (US)
Corresponding author: MARTIN, LEE J.
ORCID: SZE, CHUN-I
TRONCOSO, JUAN C.
KAWAS, CLAUDIA
MARTIN, LEE J.
Venue: Journal of Neuropathology and Experimental Neurology
Publisher: Oxford University Press (OUP)
Published: 1997-08
Volume: 56
Issue: 8
Pages: 933-944
ISSN: 0022-3069 (ISSN-L)
DOI: 10.1097/00005072-199708000-00011
OpenAlex: W2055361873
Cited by: 562
References: 0
Citations by year: 2026: 15 · 2025: 16 · 2024: 16 · 2023: 26 · 2022: 21 · 2021: 21 · 2020: 31 · 2019: 20 · 2018: 28 · 2017: 21 · 2016: 27 · 2015: 28 · 2014: 20 · 2013: 29 · 2012: 18
FWCI: 7.34
Type: journal article
Language: en
Open access: green
escholarship.org
Licence: cc-by
Locations: Journal of Neuropathology & Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: National Institutes of Health (5r35ag007914-03)
National Institute on Aging (AG07914)
National Institute of Neurological Disorders and Stroke (NS34 100, R01NS034100)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: Alzheimer's disease, synaptophysin, presynaptic vesicles, hippocampus, synaptic dysfunction, cognitive decline, amyloid plaques, neurofibrillary tangles, Braak staging, entorhinal cortex, memory impairment, synaptic membrane proteins
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Cognition Disorders, Female, Hippocampus, Humans, Male, Immunoblotting, Synaptophysin

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

Loss of the Presynaptic Vesicle Protein Synaptophysin in Hippocampus Correlates with Cognitive Decline in Alzheimer Disease

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cited by

Related

Metadata

Record

About these checks