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Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease

Abstract

The aberrant accumulation of aggregated β-amyloid peptides (Aβ) as plaques is a hallmark of Alzheimer’s disease (AD) neuropathology and reduction of Aβ has become a leading direction of emerging experimental therapies for the disease. The mechanism(s) whereby Aβ is involved in the pathophysiology of the disease remain(s) poorly understood. Initially fibrils, and subsequently oligomers of extracellular Aβ have been viewed as the most important pathogenic form of Aβ in AD. More recently, the intraneuronal accumulation of Aβ has been described in the brain, although technical considerations and its relevance in AD have made this a controversial topic. Here, we review the emerging evidence linking intraneuronal Aβ accumulation to the development of synaptic pathology and plaques in AD, and discuss the implications of intraneuronal β-amyloid for AD pathology, biology, diagnosis and therapy.

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Acknowledgments

The support of National Institutes of Health grants AG028174 and AG027140, and Alzheimer’s Association New Investigator award (D.T.) and Zenith award (G.K.G.). We thank Xun (Julie) Lian for helpful technical assistance.

Conflict of interest statement

The authors declare that they have no commercial or financial relationship that could be construed as a potential conflict of interest.

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Correspondence to Gunnar K. Gouras.

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Gouras, G.K., Tampellini, D., Takahashi, R.H. et al. Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta Neuropathol 119, 523–541 (2010). https://doi.org/10.1007/s00401-010-0679-9

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Keywords

  • Amyloid
  • Synapse
  • Tau
  • Head injury
  • Endosome
  • Dementia pugilistica