Cholinergic deafferentation of the rabbit cortex: a new animal model of A beta deposition

Brain deposition of the amyloid p-peptide (AP) is a critical step in the pa thogenesis of Alzheimer's disease (AD) and human cerebral amyloid angiopath y (CAA). A small fraction of AD and CAA cases are caused by gene mutations leading to increased production and deposition of AP, but for the majority, there is no known direct genetic cause. We have hypothesized that AP depos ition in these sporadic cases occurs as a result of cortical cholinergic de afferentation. Here we show that cortical cholinergic deafferentation, indu ced in rabbits by a selective immunotoxin, leads to Ap deposition in cerebr al blood vessels and perivascular neuropil. Biochemical measurements confir med that lesioned animals had 2.5- and 8-fold elevations of cortical A beta 40 and A beta 42, respectively. Cholinergic deafferentation may be one fac tor that can contribute to AP deposition. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.