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

Tsuyoshi Hamaguchi, Yvonne S. Eisele, Nicholas H. Varvel, Bruce Lamb, Lary C. Walker, Mathias Jucker

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalActa Neuropathologica
Volume123
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Fingerprint

Seeds
Amyloid
Brain
Amyloid beta-Protein Precursor
Transgenic Mice
Cerebral Amyloid Angiopathy
Amyloid Plaques
Prosencephalon
Peptides

Keywords

  • Alzheimer
  • Amyloid
  • Prion
  • Seeding
  • Senile plaques
  • Transgenic mouse

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

Cite this

The presence of Aβ seeds, and not age per se, is critical to the initiation of Aβ deposition in the brain. / Hamaguchi, Tsuyoshi; Eisele, Yvonne S.; Varvel, Nicholas H.; Lamb, Bruce; Walker, Lary C.; Jucker, Mathias.

In: Acta Neuropathologica, Vol. 123, No. 1, 01.2012, p. 31-37.

Research output: Contribution to journalArticle

Hamaguchi, Tsuyoshi ; Eisele, Yvonne S. ; Varvel, Nicholas H. ; Lamb, Bruce ; Walker, Lary C. ; Jucker, Mathias. / The presence of Aβ seeds, and not age per se, is critical to the initiation of Aβ deposition in the brain. In: Acta Neuropathologica. 2012 ; Vol. 123, No. 1. pp. 31-37.
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