Cited by 446Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Quantitative assessment of cortical synaptic density in Alzheimer's disease

Scheff, Stephen W., DeKosky, Steven T., Price, Douglas A.·1990·Neurobiology of Aging

DOI 10.1016/0197-4580(90)90059-9

Open this paper in CoChat — free account

Abstract

Significant progress has been made over the last decade in delineating the neuropathological and neurochemical changes in the brains of patients with Alzheimer's disease (AD). Less well studied are the actual synaptic connections of affected areas of the brain, such as the cerebral cortex. Because the final common pathway for neurotransmission involves synaptic integrity, we quantitatively assessed synaptic number and synapse size in lamina III and V of human frontal cortex (Brodmann area 9) in patients with AD and age-matched controls. Samples were also matched for postmortem interval, and artifacts associated with postmortem change were eliminated. We found a significant decrease in synaptic number per unit volume in both lamina, more marked in lamina III (-42%) than V (-29%). In both normal controls and AD brains, there was a negative correlation between synapse number and synapse size as indexed by the length of the postsynaptic density (PSD); cortical samples with fewer synapses had larger synapse size. This appeared to be a compensatory response, rather than a selective loss of small synapses, since the total amount of synaptic contact area per unit volume did not decline in lamina V (despite a 29% loss of synapses); in lamina III it was reduced 11% despite a 42% loss of synapses. The loss of synapses in AD is widespread and significant in frontal cortex; there is observable compensation by enlargement of synaptic size. This compensatory effort is overcome by the continuing loss of synapses in areas most affected by the degeneration.

Integrity signals

Registry

Crossref · 10.1016/0197-4580(90)90059-9

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

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

Claims the paper makes

This paper’s full text isn’t openly available, 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?

Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
Statistical principles in experimental design.
Winer, B. J. (1962) · McGraw-Hill Book Company · doi:10.1037/11774-000 · Cited by 27,137
Statistical Principles in Experimental Design
Myers, J. L., & Winer, B. J. (1964) · The American Journal of Psychology · doi:10.2307/1419292 · Cited by 8,111
The cholinergic hypothesis of geriatric memory dysfunction
Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982) · Science · doi:10.1126/science.7046051 · Cited by 5,545
Alzheimer's Disease: A Disorder of Cortical Cholinergic Innervation
Coyle, J. T., Price, D. L., & DeLong, M. R. (1983) · Science · doi:10.1126/science.6338589 · Cited by 3,052
Synaptic density in human frontal cortex —Developmental changes and effects of aging
Peter R., H. (1979) · Brain Research · doi:10.1016/0006-8993(79)90349-4 · Cited by 2,645
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499
The Clinical Diagnosis of Alzheimer's Disease
Wade, J. P. H., Mirsen, T. R., Hachinski, V. C., Fisman, M., Lau, C. S., & Merskey, H. (1987) · Archives of Neurology · doi:10.1001/archneur.1987.00520130016010 · Cited by 1,416
Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementa
Davies, P., Katzman, R., & Terry, R. D. (1980) · Nature · doi:10.1038/288279a0 · Cited by 882
Some morphometric aspects of the brain in senile dementia of the alzheimer type
Terry, R. D., Peck, A., DeTeresa, R., Schechter, R., & Horoupian, D. S. (1981) · Annals of Neurology · doi:10.1002/ana.410100209 · Cited by 801

Show all 41 references

Sorted by citations

Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376
Self-citation
Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease
Lue, L.-F., Kuo, Y.-M., Roher, A. E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J. H., Rydel, R. E., & Rogers, J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65184-x · Cited by 1,530
The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals
Dickerson, B. C., Bakkour, A., Salat, D. H., Feczko, E., Pacheco, J., Greve, D. N., Grodstein, F., Wright, C. I., Blacker, D., Rosas, H. D., et al. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhn113 · Cited by 1,153
Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment
Scheff, S. W., Price, D. A., Schmitt, F. A., & Mufson, E. J. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.012 · Cited by 1,017
Dendritic Spine Pathology: Cause or Consequence of Neurological Disorders?
Fiala, J. C., Spacek, J., & Harris, K. M. (2002) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00158-3 · Cited by 811
BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases
Lu, B., Nagappan, G., Guan, X.-M., Nathan, P. J., & Wren, P. B. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3505 · Cited by 763
Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer’s disease Neurons
Rajmohan, R., & Reddy, P. H. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160612 · Cited by 730
Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons
Um, J. W., Nygaard, H. B., Heiss, J. K., Kostylev, M. A., Stagi, M., Vortmeyer, A. O., Wısnıewskı, T., Gunther, E. C., & Strittmatter, S. M. (2012) · Nature Neuroscience · doi:10.1038/nn.3178 · Cited by 682
Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment
Butterfield, D. A., Reed, T., Newman, S. F., & Sultana, R. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.05.037 · Cited by 564
Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease
Roy, E. R., Wang, B., Wan, Y.-W., Chiu, G., Cole, A., Yin, Z., Propson, N. E., Xu, Y., Jankowsky, J. L., Liu, Z., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133737 · Cited by 563
Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy
Spires, T. L., Meyer-Luehmann, M., Stern, E. A., McLean, P. J., Skoch, J., Nguyen, P. T., Bacskai, B. J., & Hyman, B. T. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1879-05.2005 · Cited by 550
“In AD, synapses and dendritic spines are lost in the cortex and the hippocampus (Davies et al., 1987; de Ruiter and Uylings, 1987; Catala et al., 1988; Scheff et al., 1990; Scheff et al., 1996), and decreased cortical synapse density correlates with cognitive decline in patients (Terry et al.”
Background
Synaptic degeneration in Alzheimer's disease
Arendt, T. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0536-x · Cited by 517
Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses
Abramov, E., Dolev, I., Fogel, H., Ciccotosto, G. D., Ruff, E., & Slutsky, I. (2009) · Nature Neuroscience · doi:10.1038/nn.2433 · Cited by 499
Reduced IGF-1 signaling delays age-associated proteotoxicity in mice
Cohen, E., Paulsson, J. F., Blinder, P., Burstyn-Cohen, T., Du, D., Estepa, G., Adame, A., Pham, H. M., Holzenberger, M., Kelly, J. W., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.014 · Cited by 488
Lipid peroxidation triggers neurodegeneration: A redox proteomics view into the Alzheimer disease brain
Sultana, R., Perluigi, M., & Butterfield, D. A. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.09.027 · Cited by 478
Basal forebrain lesions in monkeys disrupt attention but not learning and memory [published erratum appears in J Neurosci 1995 Mar;15(3): following table of contents]
Voytko, M., Olton, D., Richardson, R., Gorman, L. K., Tobin, J., & Price, D. L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-01-00167.1994 · Cited by 520
Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein
Gimbel, D. A., Nygaard, H. B., Coffey, E. E., Gunther, E. C., Laurén, J., Gimbel, Z. A., & Strittmatter, S. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0395-10.2010 · Cited by 418
Correlations of synaptic and pathological markers with cognition of the elderly
Dickson, D. W., Crystal, H. A., Bevona, C., Honer, W., Vincent, I., & Davies, P. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00013-5 · Cited by 410
Looking Backward to Move Forward: Early Detection of Neurodegenerative Disorders
DeKosky, S. T., & MAREK, K. L. (2003) · Science · doi:10.1126/science.1090349 · Cited by 414
Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies
Scheff, S. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.08.002 · Cited by 391
Differential loss of synaptic proteins in Alzheimer's disease: Implications for synaptic dysfunction
Reddy, P. H., Mani, G., Park, B. S., Jacques, J., MURDOCH, G. H., Whetsell, W. O., Kaye, J. A., & Mańczak, M. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-7203 · Cited by 384
“Preclinical” AD revisited: Neuropathology of cognitively normal older adults
Schmitt, F. A., Davis, D. G., Wekstein, D. R., Smith, C. D., Ashford, J. W., & Markesbery, W. R. (2000) · Neurology · doi:10.1212/wnl.55.3.370 · Cited by 369
Synaptic slaughter in Alzheimer's disease
Coleman, P. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.09.001 · Cited by 351
Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348
Membrane Lipids, Selectively Diminished in Alzheimer Brains, Suggest Synapse Loss as a Primary Event in Early‐Onset Form (Type I) and Demyelination in Late‐Onset Form (Type II)
Svennerholm, L. T., & Gottfries, C. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.62031039.x · Cited by 327
Category-Specific Semantic Deficits in Focal and Widespread Brain Damage: A Computational Account
Devlin, J. T., Gonnerman, L. M., Andersen, E. S., & Seidenberg, M. S. (1998) · Journal of Cognitive Neuroscience · doi:10.1162/089892998563798 · Cited by 331
Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele
Arendt, T., Schindler, C., Brückner, M. K., Eschrich, K., Bigl, V., Zedlick, D., & Marcova, L. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-02-00516.1997 · Cited by 319
A focus on the synapse for neuroprotection in Alzheimer disease and other dementias
Coleman, P., Federoff, H., & Kurlan, R. (2004) · Neurology · doi:10.1212/01.wnl.0000140626.48118.0a · Cited by 314
Say NO to Alzheimer's disease: the putative links between nitric oxide and dementia of the Alzheimer's type
Law, A. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00051-5 · Cited by 314
Microtubule Reduction in Alzheimer's Disease and Aging Is Independent of τ Filament Formation
Cash, A., Aliev, G., Siedlak, S. L., Nunomura, A., Fujioka, H., Zhu, X., Raina, A. K., Vinters, H. V., Tabaton, M., Johnson, T., et al. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64296-4 · Cited by 317
In vivo measurement of widespread synaptic loss in Alzheimer’s disease with SV2A PET
Mecca, A. P., Chen, M., O'Dell, R. S., Naganawa, M., Toyonaga, T., Godek, T. A., Harris, J. E., Bartlett, H. H., Zhao, W., Nabulsi, N. B., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12097 · Cited by 288
Patterns of Motor Impairment in Normal Aging, Mild Cognitive Decline, and Early Alzheimer' Disease
Kluger, A., Gianutsos, J. G., Golomb, J. B., Ferris, S. H., GEORGE, A. E., Franssen, E., & Reisberg, ‌. (1997) · The Journals of Gerontology Series B · doi:10.1093/geronb/52b.1.p28 · Cited by 304
Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease.
Masliah, E., Terry, R. D., Alford, M. F., DeTeresa, R. M., & Hansen, L. A. (1991) · PubMed Central · Cited by 296
Alzheimer Disease Pathogenesis: Insights From Molecular and Cellular Biology Studies of Oligomeric Aβ and Tau Species
Chen, X., & Mobley, W. C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00659 · Cited by 302
Alzheimer’s disease-related alterations in synaptic density: neocortex and hippocampus.
Scheff, S. W., & Price, D. A. (2006) · Journal of Alzheimer's Disease · doi:10.3233/jad-2006-9s312 · Cited by 284
Self-citation
Meta‐analysis of synaptic pathology in Alzheimer's disease reveals selective molecular vesicular machinery vulnerability
de Wilde, M. C., Overk, C., Sijben, J., & Masliah, E. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.12.005 · Cited by 287
Pathogenic Forms of Tau Inhibit Kinesin-Dependent Axonal Transport through a Mechanism Involving Activation of Axonal Phosphotransferases
Kanaan, N. M., Morfini, G. A., LaPointe, N. E., Pigino, G. F., Patterson, K. R., Song, Y., Andreadis, A., Fu, Y., Brady, S. T., & Binder, L. I. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0560-11.2011 · Cited by 292
Synapse loss in the temporal lobe in Alzheimer's disease
Scheff, S. W., & PRICE, D. A. (1993) · Annals of Neurology · doi:10.1002/ana.410330209 · Cited by 273
Proline Isomer-Specific Antibodies Reveal the Early Pathogenic Tau Conformation in Alzheimer's Disease
Nakamura, K., Greenwood, A., Binder, L. I., Bigio, E. H., Denial, S., Nicholson, L. K., Zhou, X. Z., & Lu, K. P. (2012) · Cell · doi:10.1016/j.cell.2012.02.016 · Cited by 260
Mild cognitive impairment: pathology and mechanisms
Mufson, E. J., Binder, L. I., Counts, S., DeKosky, S. T., deToledo‐Morrell, L., Ginsberg, S. D., Ikonomović, M. D., Perez, S. E., & Scheff, S. W. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0884-1 · Cited by 268
Patterns of aberrant sprouting in alzheimer's disease
Masliah, E., Mallory, M. E., Hansen, L. A., Alford, M. F., Albright, T., DeTeresa, R. M., Terry, R. D., Baudier, J., & Saitoh, T. (1991) · Neuron · doi:10.1016/0896-6273(91)90170-5 · Cited by 243
Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer's disease neurons
Calkins, M. J., & Reddy, P. H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.01.007 · Cited by 252
Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease
Overk, C. R., & Masliah, E. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.015 · Cited by 242
4-Hydroxy-2-nonenal, a reactive product of lipid peroxidation, and neurodegenerative diseases: a toxic combination illuminated by redox proteomics studies
Perluigi, M., Coccia, R., & Butterfield, D. A. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4406 · Cited by 229
Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein.
Fagan, A. M., Bu, G., Sun, Y., Daugherty, A., & Holtzman, D. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.30121 · Cited by 226
Motor cortex excitability in Alzheimer's disease: A transcranial magnetic stimulation study
Ferreri, F., Pauri, F., Pasqualetti, P., Fini, R., Forno, G. D., & Rossini, P. M. (2002) · Annals of Neurology · doi:10.1002/ana.10416 · Cited by 223
Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations
DeKosky, S. T., Harbaugh, R. E., Schmitt, F. A., Bakay, R. A. E., Chui, H. C., Knopman, D. S., Reeder, T. M., Shetter, A. G., Senter, H. J., Markesbery, W. R., et al. (1992) · Annals of Neurology · doi:10.1002/ana.410320505 · Cited by 223
Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan
Tay, T. L., Béchade, C., D’Andrea, I., St‐Pierre, M., Henry, M. S., Roumier, A., & Tremblay, M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00421 · Cited by 217
Differential Expression of Synaptic Proteins in the Frontal and Temporal Cortex of Elderly Subjects With Mild Cognitive Impairment
Counts, S., Nadeem, M., Lad, S. P., Wuu, J., & Mufson, E. J. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-200606000-00007 · Cited by 212
The Eye As a Biomarker for Alzheimer's Disease
Lim, J. K. H., Li, Q.-X., He, Z., Vingrys, A. J., Wong, V. H. Y., Currier, N. V., Mullen, J., Bui, B. V., & Nguyen, C. T. O. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00536 · Cited by 221
Diffuse plaques do not accentuate synapse loss in Alzheimer's disease.
(1990) · Europe PMC (PubMed Central) · Cited by 209
A Close Look at BACE1 Inhibitors for Alzheimer’s Disease Treatment
Das, B., & Yan, R. (2019) · CNS Drugs · doi:10.1007/s40263-019-00613-7 · Cited by 218
Defects in expression of genes related to synaptic vesicle traffickingin frontal cortex of Alzheimer’s disease
Yao, P. J., Zhu, M., Pyun, E. I., Brooks, A. I., Therianos, S., Meyers, V. E., & Coleman, P. D. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(02)00009-8 · Cited by 216
Calcium/calmodulin-dependent kinase II and Alzheimer’s disease
Ghosh, A., & Giese, K. P. (2015) · Molecular Brain · doi:10.1186/s13041-015-0166-2 · Cited by 205
Fractionating verbal episodic memory in Alzheimer's disease
Wolk, D. A., & Dickerson, B. C. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.09.005 · Cited by 211
Synaptic oligomeric tau in Alzheimer’s disease — A potential culprit in the spread of tau pathology through the brain
Colom-Cadena, M., Davies, C., Sirisi, S., Lee, J.-E., Simzer, E. M., Tzioras, M., Querol-Vilaseca, M., Sánchez-Aced, É., Chang, Y. Y., Holt, K., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.04.020 · Cited by 224
Synapse pathology in Alzheimer’s disease
Griffiths, J., & Grant, S. G. N. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.05.028 · Cited by 212
Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression
Meftah, S., & Gan, J. (2023) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2023.1129036 · Cited by 205
Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the 'Dr. Jekyll and Mr. Hyde concept' of Alzheimer's disease or the yin and yang of neuroplasticity
Arendt, T. (2003) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2003.09.007 · Cited by 189
Heat stress-induced memory impairment is associated with neuroinflammation in mice
Lee, W., Moon, M., Kim, H. G., Lee, T. H., & Oh, M. S. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0324-6 · Cited by 195
The Lipid Peroxidation Product 4‐Hydroxynonenal Inhibits Neurite Outgrowth, Disrupts Neuronal Microtubules, and Modifies Cellular Tubulin
Neely, M. D., Sidell, K. R., Graham, D. G., & Montine, T. J. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722323.x · Cited by 186
Abnormalities of neural circuitry in Alzheimer's disease: Hippocampus and cortical cholinergic innervation
Geula, C. (1998) · Neurology · doi:10.1212/wnl.51.1_suppl_1.s18 · Cited by 184
Reimagining cholinergic therapy for Alzheimer’s disease
Giacobini, E., Cuello, A. C., & Fisher, A. (2022) · Brain · doi:10.1093/brain/awac096 · Cited by 187
Molecular Mechanisms of the Conjugated α,β-Unsaturated Carbonyl Derivatives: Relevance to Neurotoxicity and Neurodegenerative Diseases
LoPachin, R. M., Barber, D. S., & Gavin, T. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm301 · Cited by 180
Regional synaptic pathology in Alzheimer's disease
Honer, W. G., Dickson, D. W., Gleeson, J., & Davies, P. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90111-a · Cited by 179
Exploring the Pathogenesis of Alzheimer Disease in Basal Forebrain Cholinergic Neurons: Converging Insights From Alternative Hypotheses
Chen, X., & Mobley, W. C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00446 · Cited by 179
Synapse loss in dementias
Clare, R., King, V. G., Wirenfeldt, M., & Vinters, H. V. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22392 · Cited by 163
Immunoelectron microscopic study of synaptic pathology in Alzheimer's disease
Masliah, E., Hansen, L. A., Albright, T., Mallory, M. E., & Terry, R. D. (1991) · Acta Neuropathologica · doi:10.1007/bf00293464 · Cited by 175
Hippocampal plasticity during the progression of Alzheimer’s disease
Mufson, E. J., Mahady, L. J., Waters, D., Counts, S., Perez, S. E., DeKosky, S. T., Ginsberg, S. D., Ikonomović, M. D., Scheff, S. W., & Binder, L. I. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.03.006 · Cited by 184
Neuroplasticity in Alzheimer's disease
Teter, B., & Ashford, J. W. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10441 · Cited by 170
Alzheimer's disease as a disorder of mechanisms underlying structural brain self-organization
Arendt, T. (2001) · Neuroscience · doi:10.1016/s0306-4522(00)00516-9 · Cited by 172
Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex.
(1994) · PubMed Central · Cited by 169
Altered presynaptic protein NACP is associated with plaque formation and neurodegeneration in Alzheimer's disease.
Masliah, E., Iwai, A., Mallory, M. E., Uéda, K., & Saitoh, T. (1996) · Europe PMC (PubMed Central) · Cited by 168
Synaptic pathology in alzheimer's disease: Immunological data for markers of synaptic and large dense-core vesicles
Lassmann, H., Weiler, R., Fischer, P. A., Bancher, C., Jellinger, K. A., Floor, E., Danielczyk, W., SEITELBERGER, F., & Winkler, H. J. S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90003-k · Cited by 161
Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease
Haas, L. T., Salazar, S. V., Kostylev, M. A., Um, J. W., Kaufman, A. C., & Strittmatter, S. M. (2015) · Brain · doi:10.1093/brain/awv356 · Cited by 145
Targeting the Alpha 7 Nicotinic Acetylcholine Receptor to Reduce Amyloid Accumulation in Alzheimers Disease Pyramidal Neurons
D’Andrea, M. R., & Nagele, R. G. (2006) · Current Pharmaceutical Design · doi:10.2174/138161206775474224 · Cited by 147
Paradoxical Upregulation of Glutamatergic Presynaptic Boutons during Mild Cognitive Impairment
Bell, K. F. S., Bennett, D. A., & Cuello, A. C. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3269-07.2007 · Cited by 147
The Role of Synaptic Proteins in the Pathogenesis of Disorders of the Central Nervous System
Masliah, E., & Terry, R. D. (1993) · Brain Pathology · doi:10.1111/j.1750-3639.1993.tb00728.x · Cited by 145
Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer’s disease
Duits, F. H., Brinkmalm, G., Teunissen, C. E., Brinkmalm, A., Scheltens, P., Van der Flier, W. M., Zetterberg, H., & Blennow, K. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0335-x · Cited by 137
The amyloid pathology progresses in a neurotransmitter-specific manner
Bell, K. F. S., Ducatenzeiler, A., Ribeiro‐da‐Silva, A., Duff, K., Bennett, D. A., & Cuello, A. C. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.034 · Cited by 139
Synaptic remodeling during aging and in Alzheimer's disease
Masliah, E., Crews, L., & Hansen, L. (2006) · Journal of Alzheimer's Disease · doi:10.3233/jad-2006-9s311 · Cited by 132
Synaptic phosphorylated α-synuclein in dementia with Lewy bodies
Colom‐Cadena, M., Pegueroles, J., Herrmann, A. G., Henstridge, C. M., Muñoz, L., Querol‐Vilaseca, M., Martín-Paniello, C. S., Luque-Cabecerans, J., Clarimón, J., Belbin, O., et al. (2017) · Brain · doi:10.1093/brain/awx275 · Cited by 130
β-Amyloid-induced Dynamin 1 Depletion in Hippocampal Neurons
Kelly, B. L., Vassar, R. J., & Ferreira, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503259200 · Cited by 129
Synaptic deficit in the temporal cortex of partial trisomy 16 (Ts65Dn) mice
Kurt, M. A., Davies, D. C., Kidd, M., Dierssen, M., & Flórez, J. (2000) · Brain Research · doi:10.1016/s0006-8993(00)01984-3 · Cited by 130
Deficits of neuronal density in CA1 and synaptic density in the dentate gyrus, CA3 and CA1, in a mouse model of Down syndrome
Ayberk Kurt, M., Ilker Kafa, M., Dierssen, M., & Ceri Davies, D. (2004) · Brain Research · doi:10.1016/j.brainres.2004.06.075 · Cited by 126
ProNGF and Neurodegeneration in Alzheimer’s Disease
Fahnestock, M. L., & Shekari, A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00129 · Cited by 127
Alzheimer 100 – highlights in the history of Alzheimer research
Jellinger, K. A. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0578-3 · Cited by 133
Synaptic alterations in the rTg4510 mouse model of tauopathy
Kopeikina, K. J., Polydoro, M., Tai, H., Yaeger, E., Carlson, G. A., Pitstick, R., Hyman, B. T., & Spires‐Jones, T. L. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23234 · Cited by 129
Metformin activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against Amyloid-beta-induced mitochondrial dysfunction
Chiang, M., Cheng, Y., Chen, S., Yen, C., & Huang, R. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2016.08.013 · Cited by 126
Alzheimer's disease and aging: Effects on perforant pathway perikarya and synapses
Lippa, C. F., Hamos, J. E., Pulaski-Salo, D., DeGennaro, L. J., & Drachman, D. A. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90115-e · Cited by 123
ADAM-10 over-expression increases cortical synaptogenesis
Bell, K. F. S., Zheng, L., Fahrenholz, F., & Cuello, A. C. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.11.004 · Cited by 129
Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes
Haas, L. T., Salazar, S. V., Smith, L. M., Zhao, H. R., Cox, T. O., Herber, C. S., Degnan, A. P., Balakrishnan, A. S., Macor, J. E., Albright, C. F., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.023 · Cited by 121
Is synaptic loss a unique hallmark of Alzheimer’s disease?
Scheff, S. W., Neltner, J. H., & Nelson, P. T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.028 · Cited by 118
ApoE4 induces Aβ42, tau, and neuronal pathology in the hippocampus of young targeted replacement apoE4 mice
Liraz, O., Boehm-Cagan, A., & Michaelson, D. M. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-16 · Cited by 118
Mechanisms of neuronal death in brain aging and alzheimer's disease: Role of endocrine‐mediated calcium dyshomeostasis
Landfield, P. W., Thibault, O., Mazzanti, M. L., Porter, N. M., & Kerr, D. S. (1992) · Journal of Neurobiology · doi:10.1002/neu.480230914 · Cited by 118
Synaptic Dysfunction in Alzheimer’s Disease: Aβ, Tau, and Epigenetic Alterations
Li, K., Wei, Q., Liu, F., Hu, F., Xie, A., Zhu, L., & Liu, D. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0533-3 · Cited by 121
Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease
Kazim, S. F., & Iqbal, K. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0119-y · Cited by 126
Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα
Mockett, B. G., Richter, M., Abraham, W. C., & Müller, U. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00030 · Cited by 127
Synaptic Elimination in Neurological Disorders
Cardozo, P. L., de Lima, I. B. Q., Maciel, E. M. A., Silva, N. C., Dobránsky, T., & Ribeiro, F. M. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666190603170511 · Cited by 115

Authors: Scheff, S. W., DeKosky, S. T., & Price, D. A.
Affiliations: University of Kentucky (US)
Corresponding author: Scheff, Stephen W.
ORCID: DeKosky, Steven T.
Price, Douglas A.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 1990-01
Volume: 11
Issue: 1
Pages: 29-37
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/0197-4580(90)90059-9
OpenAlex: W2083752135
Cited by: 446
References: 41
Citations by year: 2026: 7 · 2025: 13 · 2024: 14 · 2023: 19 · 2022: 16 · 2021: 14 · 2020: 19 · 2019: 14 · 2018: 15 · 2017: 12 · 2016: 17 · 2015: 21 · 2014: 13 · 2013: 16 · 2012: 16
FWCI: 9.93
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Funders: University of Kentucky
National Institute on Aging (P50AG005144, AG-05144, P01AG005119, AG0 5119)
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, synaptic density, synapse size, postsynaptic density, frontal cortex, Brodmann area 9, cortical layers, synaptic loss, postmortem interval, neuropathology
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Cell Count, Cerebral Cortex, Female, Humans, Male, Middle Aged, Nerve Degeneration, Synapses, In Vitro Techniques

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

Quantitative assessment of cortical synaptic density in Alzheimer's disease

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks