Characterizing the appearance and growth of amyloid plaques in APP/ XXXX @entity19 .

@entity20933 @entity527 @entity19 @entity5219 @entity5357 @entity195
@entity527 are primarily composed of extracellular aggregates of @entity5357 ( @entity5357 ) peptide and are a pathological signature of @entity195 . However, the factors that influence the dynamics of @entity527 formation and growth in vivo are largely unknown. Using serial intravital multiphoton microscopy through a thinned-skull cranial window in APP/ @entity20933 @entity19 , we found that amyloid plaques appear and grow over a period of weeks before reaching a mature size. Growth was more prominent early after initial plaque formation: plaques grew faster in 6-month-old compared with 10-month-old @entity19 . Plaque growth rate was also size-related, as smaller plaques exhibited more rapid growth relative to larger plaques. Alterations in interstitial @entity5357 concentrations were associated with changes in plaque growth. Parallel studies using multiphoton microscopy and in vivo microdialysis revealed that pharmacological reduction of soluble extracellular @entity5357 by as little as 20-25% was associated with a dramatic decrease in plaque formation and growth. Furthermore, this small reduction in @entity5357 synthesis was sufficient to reduce @entity527 load in 6-month-old but not 10-month-old @entity19 , suggesting that treatment early in disease pathogenesis may be more effective than later treatment. In contrast to thinned-skull windows, no significant plaque growth was observed under open-skull windows, which demonstrated extensive microglial and astrocytic activation. Together, these findings indicate that individual @entity527 growth in vivo occurs over a period of weeks and may be influenced by interstitial @entity5357 concentration as well as reactive @entity5219 .
