Abstract
The basalo-cortical cholinergic system was characterized in mice expressing mutant human genes for presenilin-1 (PS1), amyloid precursor protein (APP), and combined PS/APP. Dual immunocytochemistry for ChAT and A beta revealed swollen cholinergic processes within cortical plaques in both APP and PS/APP brains by 12 months, suggesting aberrant sprouting or redistribution of cholinergic processes in response to amyloid deposition. At 8 months, cortical and subcortical ChAT activity was normal (PS/APP) or elevated (PS, APP frontal cortex), while cholinergic cell counts (nBM/SI) and receptor binding were unchanged. ChAT mRNA was up-regulated in the nBM/SI of all three transgenic lines at 8 months. The data indicate that the basal forebrain cholinergic system does not degenerate in mice expressing AD-related transgenes, even in mice with extreme amyloid load. The
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / metabolism
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Aging / physiology
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism
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Alzheimer Disease / physiopathology
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Amyloid beta-Protein Precursor / genetics*
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Amyloid beta-Protein Precursor / metabolism
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Animals
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Basal Nucleus of Meynert / enzymology
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Basal Nucleus of Meynert / growth & development
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Basal Nucleus of Meynert / pathology*
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Cell Count
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Cell Survival / genetics*
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Cerebral Cortex / enzymology
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Cerebral Cortex / growth & development
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Cerebral Cortex / pathology*
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Choline O-Acetyltransferase / genetics
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Choline O-Acetyltransferase / metabolism
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Cholinergic Fibers / metabolism
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Cholinergic Fibers / pathology*
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Immunohistochemistry
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Mice
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Mice, Transgenic / abnormalities
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Mice, Transgenic / metabolism
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism
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Nerve Degeneration / physiopathology
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Neuronal Plasticity / genetics*
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Plaque, Amyloid / genetics
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Plaque, Amyloid / metabolism
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Plaque, Amyloid / pathology
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Presenilin-1
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RNA, Messenger / metabolism
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Radioligand Assay
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Receptors, Muscarinic / drug effects
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Receptors, Muscarinic / metabolism
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Receptors, Nicotinic / drug effects
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Receptors, Nicotinic / metabolism
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Up-Regulation / genetics
Substances
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Amyloid beta-Protein Precursor
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Membrane Proteins
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PSEN1 protein, human
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Presenilin-1
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RNA, Messenger
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Receptors, Muscarinic
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Receptors, Nicotinic
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Choline O-Acetyltransferase
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Acetylcholine