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

• Type of Material: Article
• Authors: Tsuyoshi Hamaguchi, University of Tübingen; Yvonne S. Eisele, University of Tübingen; Nicholas H. Varvel, Emory University; Bruce T. Lamb, Cleveland Clinic Foundation; Lary C Walker, Emory University; Mathias Jucker, University of Tübingen
• Language: English
• Date: 2012-01-01
• Publisher: Springer (part of Springer Nature): Springer Open Choice Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Springer-Verlag.
• Final Published Version (URL): http://dx.doi.org/10.1007/s00401-011-0912-1
• Title of Journal or Parent Work: Acta Neuropathologica
• ISSN: 0001-6322
• Volume: 123
• Issue: 1
• Start Page: 31
• End Page: 37
• Grant/Funding Information: TH is recipient of a postdoctoral fellowship from the Alexander von Humboldt Foundation (Bonn, Germany).; This work was supported by grants from the Competence Network on Degenerative Dementias (BMBF-01GI0705); the BMBF in the frame of ERA-Net NEURON (MIPROTRAN); NIH RR-00165; P50AG025688; the Alzheimer’s Association (NIRG-10173099) and the CART Foundation.
• Keywords: Senile plaques; Pathology; PRIMATES; CHROMOSOME TRANSGENIC MICE; Amyloid; Neurosciences & Neurology; Clinical Neurology; ALZHEIMERS-DISEASE; DISORDERS; Seeding; Life Sciences & Biomedicine; INDUCTION; MOUSE MODELS; Neurosciences; Prion; Alzheimer; PROTEIN; AMYLOID DEPOSITION; Science & Technology; Transgenic mouse; PROTEOSTASIS
• Research Categories: Biology, Neuroscience; Health Sciences, Pathology

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.