Original Paper

Acta Neuropathologica

, Volume 123, Issue 1, pp 31-37

The presence of Aβ seeds, and not age per se, is critical to the initiation of Aβ deposition in the brain

  • Tsuyoshi HamaguchiAffiliated withDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of TübingenDZNE, German Center for Neurodegenerative Diseases
  • , Yvonne S. EiseleAffiliated withDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of TübingenDZNE, German Center for Neurodegenerative Diseases
  • , Nicholas H. VarvelAffiliated withDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of TübingenDZNE, German Center for Neurodegenerative Diseases
  • , Bruce T. LambAffiliated withThe Lerner Research Institute, The Cleveland Clinic Foundation
  • , Lary C. WalkerAffiliated withDepartment of Neurology, Yerkes National Primate Research Center, Emory University
  • , Mathias JuckerAffiliated withDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of TübingenDZNE, German Center for Neurodegenerative Diseases Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

The deposition of the β-amyloid (Aβ) peptide in senile plaques and cerebral Aβ-amyloid angiopathy can be seeded in β-amyloid precursor protein (APP)-transgenic mice by the intracerebral infusion of brain extracts containing aggregated Aβ. Previous studies of seeded β-amyloid induction have used relatively short incubation periods to dissociate seeded β-amyloid induction from endogenous β-amyloid deposition of the host, thus precluding the analysis of the impact of age and extended incubation periods on the instigation and spread of Aβ lesions in brain. In the present study using R1.40 APP-transgenic mice (which do not develop endogenous Aβ deposition up to 15 months of age) we show that: (1) seeding at 9 months of age does not induce more Aβ deposition than seeding at 3 months of age, provided that the incubation period (6 months) is the same; and (2) very long-term (12 months) incubation after a focal application of the seed results in the emergence of Aβ deposits throughout the forebrain. These findings indicate that the presence of Aβ seeds, and not the age of the host per se, is critical to the initiation of Aβ aggregation in the brain, and that Aβ deposition, actuated in one brain area, eventually spreads throughout the brain.

Keywords

Alzheimer Amyloid Prion Seeding Senile plaques Transgenic mouse