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Acta Neuropathol Commun. 2018 Mar 2;6(1):20. doi: 10.1186/s40478-018-0520-6.

Three-dimensional analysis of synapses in the transentorhinal cortex of Alzheimer's disease patients.

Author information

1
Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Pozuelo de Alarcón, 28223, Madrid, Spain.
2
Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avda Doctor Arce, 37, 28002, Madrid, Spain.
3
Depto. Psicobiología, Facultad de Psicología, Universidad Nacional de Educación a Distancia (UNED), c/Juan del Rosal, 10, 28040, Madrid, Spain.
4
Laboratorio de Neuroanatomía Humana, Facultad de Medicina, Universidad de Castilla-La Mancha, Almansa 14, 02006, Albacete, Spain.
5
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Madrid, Spain.
6
Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Pozuelo de Alarcón, 28223, Madrid, Spain. aidil@cajal.csic.es.
7
Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avda Doctor Arce, 37, 28002, Madrid, Spain. aidil@cajal.csic.es.
8
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Madrid, Spain. aidil@cajal.csic.es.

Abstract

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.

KEYWORDS:

Dementia; Electron Microscopy; FIB/SEM; Medial temporal lobe; Neuropil; Synapses

PMID:
29499755
PMCID:
PMC5834884
DOI:
10.1186/s40478-018-0520-6
[Indexed for MEDLINE]
Free PMC Article

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