FIB/SEM technology and Alzheimer's disease: Three-dimensional analysis of human cortical synapses

Lidia Blazquez-Llorca, Ángel Merchán-Pérez, José Rodrigo Rodríguez, Jorge Gascón, Javier DeFelipe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The quantification and measurement of synapses is a major goal in the study of brain organization in both health and disease. Serial section electron microscopy (EM) is the ideal method since it permits the direct quantification of crucial features such as the number of synapses per unit volume or the distribution and size of synapses. However, a major limitation is that obtaining long series of ultrathin sections is extremely time-consuming and difficult. Consequently, quantitative EM studies are scarce and the most common method employed to estimate synaptic density in the human brain is indirect, by counting at the light microscopic level immunoreactive puncta using synaptic markers. The recent development of automatic EM methods in experimental animals, such as the combination of focused ion beam milling and scanning electron microscopy (FIB/SEM), are opening new avenues. Here we explored the utility of FIB/SEM to examine the cerebral cortex of Alzheimer's disease patients. We found that FIB/SEM is an excellent tool to study in detail the ultrastructure and alterations of the synaptic organization of the human brain. Using this technology, it is possible to reconstruct different types of plaques and the surrounding neuropil to find new aspects of the pathological process associated with the disease, namely; to count the exact number and types of synapses in different regions of the plaques, to study the spatial distribution of synapses, and to analyze the morphology and nature of the various types of dystrophic neurites and amyloid deposits.

Original languageEnglish (US)
Pages (from-to)995-1013
Number of pages19
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2013


  • Amyloid-β plaques
  • asymmetric synapses
  • automatic electron microscopy
  • autopsy material
  • cerebral cortex
  • dystrophic neurites
  • symmetric synapses
  • ultrastructure

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


Dive into the research topics of 'FIB/SEM technology and Alzheimer's disease: Three-dimensional analysis of human cortical synapses'. Together they form a unique fingerprint.

Cite this