title: Long-term in vivo imaging of β-amyloid plaque appearance and growth in a mouse model of cerebral β-amyloidosis.
abstract: Extracellular deposition of the amyloid-β peptide (Aβ) in the brain parenchyma is a hallmark lesion of Alzheimer's disease (AD) and a predictive marker for the progression of preclinical to symptomatic AD. Here, we used multiphoton in vivo imaging to study Aβ plaque formation in the brains of 3- to 4-month-old APPPS1 transgenic mice over a period of 6 months. A novel head fixation system provided robust and efficient long-term tracking of single plaques over time. Results revealed an estimated rate of 35 newly formed plaques per cubic millimeter of neocortical volume per week at 4-5 months of age. At later time points (i.e., in the presence of increasing cerebral β-amyloidosis), the number of newly formed plaques decreased. On average, both newly formed and existing plaques grew at a similar growth rate of 0.3 μm (radius) per week. A solid knowledge of the dynamics of cerebral β-amyloidosis in mouse models provides a powerful tool to monitor preclinical Aβ targeting therapeutic strategies and eases the interpretation of diagnostic amyloid imaging in humans.
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: Jasmin K
authors.initials: JK
authors.lastname: Hefendehl
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Wegenast-Braun
authors.forename: Christian
authors.initials: C
authors.lastname: Liebig
authors.forename: Daniel
authors.initials: D
authors.lastname: Eicke
authors.forename: David
authors.initials: D
authors.lastname: Milford
authors.forename: Michael E
authors.initials: ME
authors.lastname: Calhoun
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kohsaka
authors.forename: Martin
authors.initials: M
authors.lastname: Eichner
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000686:Amyloidosis / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D005260:Female; D005911:Gliosis / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D036641:Microscopy, Fluorescence, Multiphoton; D058225:Plaque, Amyloid / Q000473:pathology*; D013194:Staining and Labeling
chemical_list: D016229:Amyloid beta-Peptides; D049452:Green Fluorescent Proteins