Long-Term In Vivo Imaging of β-Amyloid Plaque Appearance and Growth in a Mouse Model of Cerebral β-Amyloidosis

Extracellular deposition of the amyloid-beta peptide (A beta) 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 A beta 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 beta-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 mu m(radius) per week. A solid knowledge of the dynamics of cerebral beta-amyloidosis in mouse models provides a powerful tool to monitor preclinical A beta targeting therapeutic strategies and eases the interpretation of diagnostic amyloid imaging in humans.