August 7, 2019
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Article

3D Electron Microscopy Study of Synaptic Organization of the Normal Human Transentorhinal Cortex and Its Possible Alterations in Alzheimer's Disease

Publicated to: ENEURO. 6 (4): 1-17 - 2019-08-01 6(4), DOI: 10.1523/ENEURO.0140-19.2019

Authors:

Dominguez-Alvaro, M; Montero-Crespo, M; Blazquez-Llorca, L; DeFelipe, J; Alonso-Nanclares, L
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Affiliations

CIBER Enfermedades Neurodegenerativas - Author
CSIC - Instituto Cajal (IC) - Author
CSIC, Inst Cajal, Avda Doctor Arce 37, Madrid 28002, Spain - Author
ISCIII, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain - Author
UNED, Dept Psicobiol, Fac Psicol, C Juan del Rosal 10, Madrid 28040, Spain - Author
Univ Politecn Madrid, Lab Cajal Circuitos Cort, Ctr Tecnol Biomed, Madrid 28223, Spain - Author
Universidad Nacional de Educación a Distancia - Author
Universidad Politécnica de Madrid - Author
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Abstract

Copyright © 2019 Domínguez-Álvaro et al. The transentorhinal cortex (TEC) is an obliquely oriented cortex located in the medial temporal lobe and, together with the entorhinal cortex, is one of the first affected areas in Alzheimer's disease (AD). One of the most widely accepted hypotheses is that synaptopathy (synaptic alterations and loss) represents the major structural correlate of the cognitive decline observed in AD. However, very few electron microscope (EM) studies are available; the most common method to estimate synaptic density indirectly is by counting, at the light microscopic level, immunoreactive puncta using synaptic markers. To investigate synaptic morphology and possible alterations related to AD, a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning EM (FIB/SEM) was performed in the neuropil of Layer II of the TEC in human brain samples from non-demented subjects and AD patients. Evaluation of the proportion and shape of asymmetric synapses (AS) and symmetric synapses (SS) targeting spines or dendritic shafts was performed using 3D reconstructions of every synapse. The 3D analysis of 4722 synapses revealed that the preferable targets were spine heads for AS and dendritic shafts for SS, both in control and AD cases. However, in AD patients, we observed a reduction in the percentage of synapses targeting spine heads. Regarding the shape of synapses, in both control cases and AD samples, the vast majority of synapses had a macular shape, followed by perforated or horseshoe-shaped synapses, with fragmented synapses being the least frequent type. Moreover, comparisons showed an increased number of fragmented AS in AD patients.
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Keywords

AdultAged, 80 and overAlzheimer diseaseAmpaAmyloid-betaAxospinous synapsesCerebral-cortexDementiaDendritic shaftsDendritic spine pathologyDendritic spinesEntorhinal cortexFemaleFib/semHumansImaging, three-dimensionalInductionLong-term potentiationMaleMicroscopy, electronMiddle agedNmda receptorsNumberSegmented postsynaptic densitiesSynapsesSynaptic morphology

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal ENEURO due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous). Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.44. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.87 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-27, the following number of citations:

  • WoS: 37
  • Scopus: 38
  • Europe PMC: 31
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-27:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 49.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 48 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 15.
  • The number of mentions on the social network X (formerly Twitter): 9 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://oa.upm.es/85527/

As a result of the publication of the work in the institutional repository, statistical usage data has been obtained that reflects its impact. In terms of dissemination, we can state that, as of

  • Views: 158
  • Downloads: 73
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Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (DOMÍNGUEZ ÁLVARO, MARTA) and Last Author (ALONSO NANCLARES, LIDIA).

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