Telomere shortening reduces Alzheimer's disease amyloid pathology in mice

Rolyan H, Scheffold A, Heinrich A, Begus-Nahrmann Y, Langkopf BH, Hoelter SM, Vogt-Weisenhorn DM, Liss B, Wurst W, Lie DC, Thal DR, Biber K, Rudolph KL (2011)

Publication Type: Journal article

Publication year: 2011

Journal

Brain Oxford University Press

Book Volume: 134

Pages Range: 2044-56

Journal Issue: Pt 7

DOI: 10.1093/brain/awr133

Abstract

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.

Authors with CRIS profile

Dieter Chichung Lie Institut für Biochemie

Involved external institutions

Universität Ulm DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Rolyan, H., Scheffold, A., Heinrich, A., Begus-Nahrmann, Y., Langkopf, B.H., Hoelter, S.M.,... Rudolph, K.L. (2011). Telomere shortening reduces Alzheimer's disease amyloid pathology in mice. Brain, 134(Pt 7), 2044-56. https://doi.org/10.1093/brain/awr133

MLA:

Rolyan, Harshvardhan, et al. "Telomere shortening reduces Alzheimer's disease amyloid pathology in mice." Brain 134.Pt 7 (2011): 2044-56.

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