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Neuron-specific alterations in signal transduction pathways associated with Alzheimer's disease
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The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intracellular neurofibrillary tangles (NFTs), and neuronal death. Hyperphosphorylation of tau is a key factor in the generation of NFTs. Mitogen activated protein kinase 1 (MAPK1) and protein kinase C beta (PRKCB) are thought to play a role in hyperphosphorylation, and PRCKB is thought to be involved in hypoxic stress and vascular dysfunction, and to trigger MAPK phosphorylation pathways. We performed single-cell analyses of neurons with different vulnerabilities to AD-related changes. Using quantitative PCR (qPCR), we measured the levels of MAPK1 and PRKCB transcript in CA1 (high vulnerability), CA2 pyramidal cells from the hippocampus, granule cells from the cerebellum (low vulnerability), and neurons from the brain stem (nucleus tractus spinalis nervi trigemini, characterized by early neurophysiological deficits) at progressive Braak stages compared to age-matched controls. The highly vulnerable CA1 pyramidal neurons were characterized by age- and disease-unrelated increases in PRCKB levels and by age- and disease-related increases in MAPK1 levels. In contrast, low PRKCB levels were found in CA2 pyramidal neurons, and MAPK1 levels were elevated in controls and intermediate AD stages. Both PRKCB and MAPK1 were increased in the late AD stages. MAPK1 and PRKCB levels were low in the brainstem and cerebellum. We propose that alterations in the expression of these two genes occur early in the pathogenesis of AD in a region-specific manner. In addition, multiple signal transduction pathways need to be affected to result in AD instead of physiological aging.
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GERSCHÜTZ, Anne, HEINSEN, Helmut, GRÜNBLATT, Edna, WAGNER, Anne kristin, BARTL, Jasmin, MEISSNER, Christoph, FALLGATTER, Andreas j., AL-SARRAJ, Safa, TROAKES, Claire, FERRER, Isidro (ferrer abizanda), ARZBERGER, Thomas, DECKERT, Jürgen, RIEDERER, Peter, FISCHER, Matthias, TATSCHNER, Thomas, MONORANU, Camelia maria. Neuron-specific alterations in signal transduction pathways associated with Alzheimer's disease. _Journal of Alzheimer's Disease_. 2014. Vol. 40, núm. 1, pàgs. 135-142. [consulta: 28 de gener de 2026]. ISSN: 1387-2877. [Disponible a: https://hdl.handle.net/2445/172895]