Three-dimensional analysis of synapses in the transentorhinal cortex of Alzheimer’s disease patients
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Synaptic dysfunction or loss in early stages of Alzheimer's disease (AD) is thought to be a major structural correlate of cognitive dysfunction. Early loss of episodic memory, which occurs at the early stage of AD, is closely associated with the progressive degeneration of medial temporal lobe (MTL) structures of which the transentorhinal cortex (TEC) is the first affected area. However, no ultrastructural studies have been performed in this region in human brain samples from AD patients. In the present study, we have performed a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM) to investigate possible synaptic alterations in the TEC of patients with AD. Surprisingly, the analysis of the density, morphological features and spatial distribution of synapses in the neuropil showed no significant differences between AD and control samples. However, light microscopy studies showed that cortical thickness of the TEC was severely reduced in AD samples, but there were no changes in the volume occupied by neuronal and glial cell bodies, blood vessels, and neuropil. Thus, the present results indicate that there is a dramatic loss of absolute number of synapses, while the morphology of synaptic junctions and synaptic spatial distribution are maintained. How these changes affect cognitive impairment in AD remains to be elucidated.
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The use of a lower concentration of potassium ferrocyanide (0.1%) shows an improvement in membrane visualization while still allowing the PSD of the SS to be identified.
“In conclusion, the use of a lower concentration of potassium ferrocyanide (0.1%), as we propose here, shows an improvement in membrane visualization, while still allowing the PSD of the SS to be identified (Domínguez-Álvaro et al., 2018, 2019, 2021a,b; Montero-Crespo et al., 2020, 2021; Cano-Astorga et al., 2021, 2023).”
From Unambiguous identification of asymmetric and symmetric synapses using volume electron microscopy (2024) · cites this paper as Domínguez-Álvaro et al., 2018
The Electron microscopy methods (page not available) specify 0.1% potassium ferrocyanide, and the Synaptic three-dimensional analysis methods and Synaptic density results say that symmetric synapses could be identified by their thin postsynaptic density. The paper does not report a comparison showing that this concentration improved membrane visualization. (LLM, conf=0.85)
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Pickett, E. K., Rose, J. L., McCrory, C., McKenzie, C.-A., King, D., Smith, C., Gillingwater, T. H., Henstridge, C. M., & Spires‐Jones, T. L. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1903-2 · Cited by 128 · see citing works
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Self-citationTau Oligomer–Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease
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Additional file 4 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638869
Additional file 12 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638893
Criado‐Marrero, M., Gebru, N. T., Blazier, D. M., Gould, L. A., Baker, J. D., Beaulieu‐Abdelahad, D., & Blair, L. J. (2021) · Figshare · doi:10.6084/m9.figshare.14391487
Additional file 9 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638884
Additional file 5 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638872
Additional file 7 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638878
Additional file 10 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638887
Additional file 6 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638875
Wang, W., Zhao, F., Lu, Y., Siedlak, S. L., Fujioka, H., Feng, H., Perry, G., & Zhu, X. (2024) · Figshare · doi:10.6084/m9.figshare.26579702
Additional file 8 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638881
Additional file 3 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638863
Additional file 13 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638896
Additional file 2 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.24550321
Additional file 1 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2023) · Figshare · doi:10.6084/m9.figshare.24550055
Additional file 11 of Expression profiles of the autism-related SHANK proteins in the human brain
Woelfle, S., Pedro, M. T., Wagner, J., Schön, M., & Boeckers, T. M. (2024) · Figshare · doi:10.6084/m9.figshare.26638890
Dallere, S., Mattioni, A., Turégano-López, M., Blázquez‐Llorca, L., Merchán-Pérez, Á., Schellino, R., Vercelli, A., DeFelipe, J., & Boido, M. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01814-7
Self-citationDigging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis
Dallere, S., Migheli, A., & Vercelli, A. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01676-z
Guo, J., Zhang, Y., Zhai, H., Yan, H., Liu, J., & Han, H. (2026) · Expert Systems with Applications · doi:10.1016/j.eswa.2026.133467
The Adult Neurogenesis Theory of Alzheimer’s Disease Predicts Where Tauopathy Develops in the Brain
Abbate, C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198776
- Authors
- Domínguez-Álvaro, M., Montero-Crespo, M., Blazquez-Llorca, L., Insausti, R., DeFelipe, J., & Alonso-Nanclares, L.
- Affiliations
- Universidad Politécnica de Madrid (ES)
- University of Castilla-La Mancha (ES)
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- Acta Neuropathologica Communications
- Published
- 2018-03-02
- Volume
- 6
- Issue
- 1
- Pages
- 20-20
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC5834884
- OpenAlex
- W2791998342
- Cited by
- 79
- References
- 92
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 17 · 2023: 11 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 5 · 2018: 3
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Economía y Competitividad (SAF 2015-66603-P)
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CB06/05/0066)
- Alzheimer’s Association (ZEN-15-321663)
- Horizon 2020 (No. 720270)
- Ministerio de Educación, Cultura y Deporte (FPU 14/02245)
- Topics
- Health Sciences › Medicine › Physiology › 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, transentorhinal cortex, synapses, synaptic ultrastructure, synaptic loss, cortical thinning, three-dimensional ultrastructure, FIB-SEM, cognitive impairment
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, Female, Humans, Immunohistochemistry, Male, Microscopy, Electron, Scanning, Middle Aged, Neuroglia, Organ Size, Synapses, User-Computer Interface, Imaging, Three-Dimensional
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