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Palop JJ, Jones B, Kekonius L, Chin J, Yu GQ, Raber J, Masliah E, Mucke L. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9572-7. Epub 2003 Jul 24 PubMed.
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Yale University School of Medicine
Amyloid peptide-induced behavioral deficits in transgenic models of Alzheimer's disease are tightly linked to depletion of calcium-dependent proteins in granule cells of the dentate gyrus.
This work builds on earlier observations that described the reduction in levels of calbindin D28K, a high-affinity calcium-binding protein, in the brains of patients with various neurodegenerative diseases.
Transgenic mice carrying mutant forms of human APP accumulate amyloid plaques and exhibit learning deficits. Careful immunochemical studies show that there are also significant reductions in the levels of calbindin D28K (CB) and c-Fos in the brains of these mice, and that these seem to correlate more with the levels of soluble Ab peptide levels in brain extracts than with the amount of accumulated amyloid plaque. Reduced levels of CB were also found in brain samples from patients with AD.
The strength of this study is the careful correlation of learning defects in genetically manipulated mice that show age-dependent
View all comments by Vincent Marchesichanges in the amounts of a well-defined calcium-binding protein. Those changes correlate, albeit roughly, with Ab peptide levels rather than with recognizable plaque material. The results are consistent with the possibility that reduced levels of calcium "buffering" capacity may cause affected neurons to be more sensitive to calcium-induced cell death. The basis for the reduced levels of CB have not been determined, but the authors note that reduced CB levels could prove to be a useful surrogate marker for the detection of incipient forms of neurodegeneration.
Université Libre de Bruxelles Faculty of Medicine
I would like to stress that already in 1993, Sutherland MK, Wong L, Somerville MJ, Yoong LK, Bergeron C, Parmentier M, McLachlan DR published in Brain Res Mol Brain Res. 1993 Apr;18(1-2):32-42 Reduction of calbindin-28k mRNA levels in Alzheimer as compared to Huntington hippocampus. Indeed the correlation between learning deficit and calbinbin is indeed appealing and deserve further experiments. What about cross breeding knock out mice for calbindin and APP transgenic mice?
View all comments by Roland PochetMake a Comment
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