Cortical cholinergic denervation elicits vascular A beta deposition.
Selective destruction of the cholinergic nucleus basalis magnocellularis (nbm) in the rabbit by the p75 neurotrophin receptor (NTR) immunoglobulin G (IgG) complexed to the toxin saporin leads to the deposition of amyloid-beta (A beta) in and around cerebral blood vessels. In some instances, the perivascular A beta resemble the diffuse deposits observed in Alzheimer's disease (AD). We propose that cortical cholinergic deprivation results, among other perturbations, in the loss of vasodilation mediated by acetylcholine. In addition to a dysfunctional cerebral blood flow, alterations in vascular chemistry affecting endothelial and smooth muscle cells may result in cerebral hypoperfusion and a breached blood-brain barrier (BBB). The selective removal of the rabbit nbm and A beta accumulation may serve as an important nontransgenic, and more physiological, model for the testing of pharmacological and immunological agents designed to control the deposition and the deleterious effects of A beta in AD.
Roher
A E
AE
Sun Health Research Institute, Sun City, Arizona 85351, USA. aroher@mail.sunhealth.org
Kuo
Y M
YM
Potter
P E
PE
Emmerling
M R
MR
Durham
R A
RA
Walker
D G
DG
Sue
L I
LI
Honer
W G
WG
Beach
T G
TG
D000109:Acetylcholine / Q000502:physiology; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D020532:Basal Nucleus of Meynert / Q000473:pathology / Q000503:physiopathology; D001812:Blood-Brain Barrier; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D007839:Functional Laterality; D007074:Immunoglobulin G; D000922:Immunotoxins / Q000633:toxicity*; D007276:Injections, Intraventricular; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D012039:Regional Blood Flow; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000922:Immunotoxins; D010940:Plant Proteins; D017475:Receptors, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine