Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / physiology
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / blood
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Amyloid beta-Peptides / metabolism*
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Animals
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Antibodies, Monoclonal
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Basal Nucleus of Meynert / pathology
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Basal Nucleus of Meynert / physiopathology
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Blood-Brain Barrier
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Cerebral Cortex / blood supply
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Cerebral Cortex / pathology*
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Cerebral Cortex / physiopathology
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Cerebral Ventricles / drug effects
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Cerebral Ventricles / physiology
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Cerebrovascular Circulation / drug effects
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Cerebrovascular Circulation / physiology*
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Denervation
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Functional Laterality
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Immunoglobulin G
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Immunotoxins / toxicity*
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Injections, Intraventricular
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Microcirculation / drug effects
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Microcirculation / metabolism
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Microcirculation / pathology*
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N-Glycosyl Hydrolases*
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Plant Proteins / administration & dosage
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Plant Proteins / toxicity*
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Rabbits
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Receptors, Nerve Growth Factor / antagonists & inhibitors
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Receptors, Nerve Growth Factor / physiology*
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Regional Blood Flow
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Ribosome Inactivating Proteins, Type 1
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Saporins
Substances
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Amyloid beta-Peptides
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Antibodies, Monoclonal
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Immunoglobulin G
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Immunotoxins
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Plant Proteins
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Receptors, Nerve Growth Factor
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Ribosome Inactivating Proteins, Type 1
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N-Glycosyl Hydrolases
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Saporins
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Acetylcholine