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

Neurosci Lett. 2000 Mar 31;283(1):9-12. doi: 10.1016/s0304-3940(00)00916-2.


Brain deposition of the amyloid beta-peptide (Abeta) 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 Abeta, but for the majority, there is no known direct genetic cause. We have hypothesized that Abeta 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 Abeta deposition in cerebral blood vessels and perivascular neuropil. Biochemical measurements confirmed that lesioned animals had 2.5- and 8-fold elevations of cortical Abeta40 and Abeta42, respectively. Cholinergic deafferentation may be one factor that can contribute to Abeta deposition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / drug effects
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Basal Nucleus of Meynert / drug effects
  • Basal Nucleus of Meynert / pathology
  • Basal Nucleus of Meynert / physiopathology
  • Cerebral Amyloid Angiopathy / physiopathology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiopathology*
  • Choline O-Acetyltransferase / drug effects
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Fibers / drug effects*
  • Cholinergic Fibers / metabolism*
  • Cholinergic Fibers / pathology
  • Denervation
  • Disease Models, Animal
  • Immunotoxins / pharmacology
  • Nerve Degeneration / chemically induced*
  • Neurons / drug effects
  • Neurons / pathology
  • Neurotoxins / pharmacology
  • Rabbits


  • Amyloid beta-Peptides
  • Immunotoxins
  • Neurotoxins
  • Choline O-Acetyltransferase