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Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice.
Neuroscience. 2004; 125(4):1009-17.N

Abstract

Alzheimer's disease is characterized by amyloid peptide formation and deposition, neurofibrillary tangles, central cholinergic dysfunction, and dementia; however, the relationship between these parameters is not well understood. We studied the effect of amyloid peptide formation and deposition on central cholinergic function in knock-in mice carrying the human amyloid precursor protein (APP) gene with the Swedish/London double mutation (APP-SL mice) which were crossbred with transgenic mice overexpressing normal (PS1wt) or mutated (M146L; PS1mut) human presenilin-1. APP-SLxPS1mut mice had increased levels of Abeta peptides at 10 months of age and amyloid plaques at 14 months of age while APP-SLxPS1wt mice did not have increased peptide levels and did not develop amyloid plaques. We used microdialysis in 15-27 months old mice to compare hippocampal acetylcholine (ACh) levels in the two mouse lines and found that extracellular ACh levels were slightly but significantly reduced in the APP-SLxPS1mut mice (-26%; P=0.044). Exploratory activity in the open field increased hippocampal ACh release by two-fold in both mouse lines; total and relative increases were not significantly different for the two strains under study. Similarly, infusion of scopolamine (1 microM) increased hippocampal ACh release to a similar extent (3-5-fold) in both groups. High-affinity choline uptake, a measure of the ACh turnover rate, was identical in both mouse lines. Neurons expressing choline acetyltransferase were increased in the septum of APP-SLxPS1mut mice (+26%; P=0.046). We conclude that amyloid peptide production causes a small decrease of extracellular ACh levels. The deposition of amyloid plaques, however, does not impair stimulated ACh release and proceeds without major changes of central cholinergic function.

Authors+Show Affiliations

Alzheimer Research Group, Bayer Health Care AG, D-42096 Wuppertal, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15120860

Citation

Hartmann, J, et al. "Central Cholinergic Functions in Human Amyloid Precursor Protein Knock-in/presenilin-1 Transgenic Mice." Neuroscience, vol. 125, no. 4, 2004, pp. 1009-17.
Hartmann J, Erb C, Ebert U, et al. Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice. Neuroscience. 2004;125(4):1009-17.
Hartmann, J., Erb, C., Ebert, U., Baumann, K. H., Popp, A., König, G., & Klein, J. (2004). Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice. Neuroscience, 125(4), 1009-17.
Hartmann J, et al. Central Cholinergic Functions in Human Amyloid Precursor Protein Knock-in/presenilin-1 Transgenic Mice. Neuroscience. 2004;125(4):1009-17. PubMed PMID: 15120860.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice. AU - Hartmann,J, AU - Erb,C, AU - Ebert,U, AU - Baumann,K H, AU - Popp,A, AU - König,G, AU - Klein,J, PY - 2004/02/26/accepted PY - 2004/5/4/pubmed PY - 2004/8/3/medline PY - 2004/5/4/entrez SP - 1009 EP - 17 JF - Neuroscience JO - Neuroscience VL - 125 IS - 4 N2 - Alzheimer's disease is characterized by amyloid peptide formation and deposition, neurofibrillary tangles, central cholinergic dysfunction, and dementia; however, the relationship between these parameters is not well understood. We studied the effect of amyloid peptide formation and deposition on central cholinergic function in knock-in mice carrying the human amyloid precursor protein (APP) gene with the Swedish/London double mutation (APP-SL mice) which were crossbred with transgenic mice overexpressing normal (PS1wt) or mutated (M146L; PS1mut) human presenilin-1. APP-SLxPS1mut mice had increased levels of Abeta peptides at 10 months of age and amyloid plaques at 14 months of age while APP-SLxPS1wt mice did not have increased peptide levels and did not develop amyloid plaques. We used microdialysis in 15-27 months old mice to compare hippocampal acetylcholine (ACh) levels in the two mouse lines and found that extracellular ACh levels were slightly but significantly reduced in the APP-SLxPS1mut mice (-26%; P=0.044). Exploratory activity in the open field increased hippocampal ACh release by two-fold in both mouse lines; total and relative increases were not significantly different for the two strains under study. Similarly, infusion of scopolamine (1 microM) increased hippocampal ACh release to a similar extent (3-5-fold) in both groups. High-affinity choline uptake, a measure of the ACh turnover rate, was identical in both mouse lines. Neurons expressing choline acetyltransferase were increased in the septum of APP-SLxPS1mut mice (+26%; P=0.046). We conclude that amyloid peptide production causes a small decrease of extracellular ACh levels. The deposition of amyloid plaques, however, does not impair stimulated ACh release and proceeds without major changes of central cholinergic function. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/15120860/Central_cholinergic_functions_in_human_amyloid_precursor_protein_knock_in/presenilin_1_transgenic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306452204001629 DB - PRIME DP - Unbound Medicine ER -