Telomere shortening reduces Alzheimer's disease amyloid pathology in mice
| Autor: | Wolfgang Wurst, Yvonne Begus-Nahrmann, Knut Biber, Annika Scheffold, Britta Heike Langkopf, Dieter Chichung Lie, Annette Heinrich, Daniela Vogt-Weisenhorn, Karl Lenhard Rudolph, Dietmar Rudolf Thal, Sabine M. Hölter, Harshvardhan Rolyan, Birgit Liss |
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| Přispěvatelé: | Molecular Neuroscience and Ageing Research (MOLAR) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Doublecortin Domain Proteins
Telomerase Pathology BLOOD-CELLS microglia Plaque Amyloid Hippocampus Amyloid beta-Protein Precursor Mice Aspartic Acid Endopeptidases Senile plaques LIFE-SPAN Cerebral Cortex Neurons TRANSGENIC MICE Cell Cycle Microfilament Proteins Neurogenesis Age Factors Telomere Alzheimer's disease adult neurogenesis ADULT HIPPOCAMPAL NEUROGENESIS Microtubule-Associated Proteins medicine.medical_specialty amyloid plaques Mice Transgenic Biology Presenilin Microscopy Electron Transmission Alzheimer Disease Internal medicine Presenilin-1 medicine Animals Maze Learning Amyloid beta-Peptides Dentate gyrus Calcium-Binding Proteins Neuropeptides INFLAMMATORY RESPONSE MICROGLIAL CELLS STEM-CELL FUNCTION medicine.disease telomeres Mice Inbred C57BL Disease Models Animal Endocrinology Bromodeoxyuridine DNA-DAMAGE DENTATE GYRUS Ageing ageing Synapses DNA damage IMMUNE-SYSTEM Neurology (clinical) Amyloid Precursor Protein Secretases Cognition Disorders |
| Zdroj: | Brain, 134, 2044-2056. Oxford University Press |
| ISSN: | 0006-8950 |
| DOI: | 10.1093/brain/awr133 |
| Popis: | Alzheimer's disease is a neurodegenerative disorder of the elderly and advancing age is the major risk factor for Alzheimer's disease development. Telomere shortening represents one of the molecular causes of ageing that limits the proliferative capacity of cells, including neural stem cells. Studies on telomere lengths in patients with Alzheimer's disease have revealed contrary results and the functional role of telomere shortening on brain ageing and Alzheimer's disease is not known. Here, we have investigated the effects of telomere shortening on adult neurogenesis and Alzheimer's disease progression in mice. The study shows that aged telomerase knockout mice with short telomeres (G3Terc(-/-)) exhibit reduced dentate gyrus neurogenesis and loss of neurons in hippocampus and frontal cortex, associated with short-term memory deficit in comparison to mice with long telomere reserves (Terc(+/+)). In contrast, telomere shortening improved the spatial learning ability of ageing APP23 transgenic mice, a mouse model for Alzheimer's disease. Telomere shortening was also associated with an activation of microglia in ageing amyloid-free brain. However, in APP23 transgenic mice, telomere shortening reduced both amyloid plaque pathology and reactive microgliosis. Together, these results provide the first experimental evidence that telomere shortening, despite impairing adult neurogenesis and maintenance of post-mitotic neurons, can slow down the progression of amyloid plaque pathology in Alzheimer's disease, possibly involving telomere-dependent effects on microglia activation. |
| Databáze: | OpenAIRE |
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