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Alzheimer's Disease: Overview01:26

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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
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Updated: Feb 22, 2026

Correlative Light and Electron Microscopy to Study Microglial Interactions with &#946;-Amyloid Plaques
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Digging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis.

Sveva Dallere1,2, Antonio Migheli3, Alessandro Vercelli4

  • 1Department of Neuroscience "Rita Levi Montalcini", Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Regione Gonzole 10, 10043, Orbassano, Turin, Italy.

Cellular and Molecular Neurobiology
|February 20, 2026
PubMed
Summary
This summary is machine-generated.

Electron microscopy (EM) is crucial for understanding Alzheimer disease (AD) at the subcellular level. Advanced EM techniques reveal detailed pathology, aiding in the development of new therapeutic strategies for this neurodegenerative disorder.

Keywords:
Alzheimer diseaseBeta amyloidDiagnosticsElectron microscopyHyperphosphorylated tauNeuropathology

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Area of Science:

  • Neuroscience
  • Pathology
  • Biophysics

Background:

  • Alzheimer disease (AD) is a progressive neurodegenerative disorder with no cure.
  • Understanding subcellular alterations is key to elucidating AD mechanisms and developing treatments.
  • Electron microscopy (EM) has historically been vital in characterizing AD pathology.

Purpose of the Study:

  • To review the state of knowledge on EM-based studies in Alzheimer disease.
  • To emphasize the central role of EM in advancing mechanistic understanding and translational approaches for AD.
  • To highlight how EM reveals subcellular alterations critical for AD pathogenesis.

Main Methods:

  • Review of conventional transmission and scanning EM studies.
  • Integration of advanced EM techniques: volume EM (vEM), cryo-electron microscopy (cryo-EM), and cryo-electron tomography (cryo-ET).
  • Analysis of EM data from human tissues, animal models, cell cultures, and synthetic assemblies.

Main Results:

  • EM has characterized key AD ultrastructures like amyloid-beta (Aβ) deposits and paired helical filaments (PHFs).
  • Advanced EM techniques provide near-native, near-atomic resolution 3D reconstructions of AD pathology.
  • EM has identified the contribution of various subcellular compartments (synapses, mitochondria, lysosomes, etc.) to AD pathogenesis.

Conclusions:

  • EM is an indispensable tool for dissecting AD disease mechanisms at the subcellular level.
  • EM provides a comprehensive view of the AD subcellular landscape, essential for therapeutic development.
  • EM studies facilitate cross-system comparisons, highlighting conserved pathological features and guiding rational drug design.