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

Brain deposition of the amyloid β-peptide (Aβ) is a critical step in the pathogenesis of Alzheimer's disease (AD) and human cerebral amyloid angiopathy (CAA). A small fraction of AD and CAA cases are caused by gene mutations leading to increased production and deposition of Aβ, but for the majority, there is no known direct genetic cause. We have hypothesized that Aβ deposition in these sporadic cases occurs as a result of cortical cholinergic deafferentation. Here we show that cortical cholinergic deafferentation, induced in rabbits by a selective immunotoxin, leads to Aβ deposition in cerebral blood vessels and perivascular neuropil. Biochemical measurements confirmed that lesioned animals had 2.5- and 8-fold elevations of cortical Aβ40 and Aβ42, respectively. Cholinergic deafferentation may be one factor that can contribute to Aβ deposition.