title: Loss of Calbindin immunoreactivity in the dentate gyrus distinguishes Alzheimer's disease from other neurodegenerative dementias.
abstract: Calbindin (Cb) is one of the major Ca(2+) binding proteins exhibiting neuromodulatory functions such as long-term potentiation (LTP), synaptic plasticity, and memory functions. It is expressed in hippocampal interneurons, pyramidal cells and granule cells of the dentate gyrus (DGCs). Cb mRNA levels remain stable during normal ageing, but decrease in Alzheimer's, Huntington, and Parkinson's disease. A recent study suggested a link between Aβ-induced Alzheimer's disease (AD)-related cognitive deficits and neuronal depletion of Cb. To evaluate whether this is specific for AD, we performed a comparative study of Cb immunoreactivity of DGCs in cases with AD-related neuropathologic change (49), grouped according to the stages of Braak and Braak, BB), Creutzfeldt-Jakob-disease (16), FTLD-tau Pick's disease type (PiD; 5), argyrophilic grain disease (8), and FTLD-TDP types A and B (6). The group of AD cases with BB stages V and VI showed the highest proportion of Cb negative cells in the DGC when compared to all other groups except PiD. The ratio of negative cells correlated significantly with the BB stages. While the total number of DGCs decreased with age in our series, loss of Cb immunoreactivity was shown to be age-dependent only in PiD and FTLD-TDP. We conclude, that late stage AD-neuropathologic change (BB V and VI stages) associates with significantly higher ratios of Cb negative DGCs and this correlates with advanced BB stage. This might suggest an accumulative effect of an epilepsy-like pathway on the Cb expression or the direct influence of local pathological protein deposits on the DGCs.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Department of Neurosurgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Stefanits
authors.affiliation: Institute of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Wesseling
authors.affiliation: Institute of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: gabor.kovacs@meduniwien.ac.at.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D064026:Calbindins / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology
chemical_list: D064026:Calbindins
keywords: Alzheimer’s disease; Calbindin; Dentate gyrus; Granule cells