Cited by 235Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities

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Dorostkar, Mario M., Zou, Chengyu, Blazquez-Llorca, Lidia, Herms, Jochen·2015·Acta Neuropathologica

Abstract

Synaptic failure is an immediate cause of cognitive decline and memory dysfunction in Alzheimer's disease. Dendritic spines are specialized structures on neuronal processes, on which excitatory synaptic contacts take place and the loss of dendritic spines directly correlates with the loss of synaptic function. Dendritic spines are readily accessible for both in vitro and in vivo experiments and have, therefore, been studied in great detail in Alzheimer's disease mouse models. To date, a large number of different mechanisms have been proposed to cause dendritic spine dysfunction and loss in Alzheimer's disease. For instance, amyloid beta fibrils, diffusible oligomers or the intracellular accumulation of amyloid beta have been found to alter the function and structure of dendritic spines by distinct mechanisms. Furthermore, tau hyperphosphorylation and microglia activation, which are thought to be consequences of amyloidosis in Alzheimer's disease, may also contribute to spine loss. Lastly, genetic and therapeutic interventions employed to model the disease and elucidate its pathogenetic mechanisms in experimental animals may cause alterations of dendritic spines on their own. However, to date none of these mechanisms have been translated into successful therapeutic approaches for the human disease. Here, we critically review the most intensely studied mechanisms of spine loss in Alzheimer's disease as well as the possible pitfalls inherent in the animal models of such a complex neurodegenerative disorder.

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  1. [133]Mori C Spooner ET Wisniewsk KE Wisniewski TM Yamaguch H Saido TC Tolan DR Selkoe DJ Lemere CA Intraneuronal Abeta42 accumulation in Down syndrome brain Amyloid 2002 9 88 102 12440481

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Authors
Dorostkar, M. M., Zou, C., Blazquez-Llorca, L., & Herms, J.
Affiliations
  • Institut für Neuropathologie (DE)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
Herms, Jochen
Venue
Acta Neuropathologica
Published
2015-06-11
Volume
130
Issue
1
Pages
1-19
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
OpenAlex
W622376569
Cited by
235
References
232
Citations by year
2026: 15 · 2025: 30 · 2024: 34 · 2023: 20 · 2022: 25 · 2021: 29 · 2020: 23 · 2019: 19 · 2018: 13 · 2017: 13 · 2016: 12 · 2015: 2
FWCI
1.59
Type
journal article
Language
en
Open access
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DZNE Pub (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
dendritic spine loss, Alzheimer's disease, synaptic dysfunction, amyloid-beta, amyloid oligomers, tau hyperphosphorylation, microglial activation, animal models of Alzheimer's disease, cognitive decline, memory impairment
MeSH terms
Alzheimer Disease, Amyloid, Animals, Brain, Humans, Dendritic Spines

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