APP and Alzheimer disease: In accordance with the classical observation that soluble radiolabeled Aβ(1–40) is accumulated on SPs in frozen tissue sections from AD brains in vitro [30], it has been shown that exogenous administration of soluble radiolabeled Aβ(1–40) into the brains significantly lowers the recovery rate of Aβ in the ISF of plaque-rich APP tg mice compared with that in plaque-free mice [21].