Memory deficits correlate with tau and spine pathology in P301S MAPT transgenic mice
Article first published online: 17 NOV 2014
© 2014 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 40, Issue 7, pages 833–843, December 2014
How to Cite
Xu, H., Rösler, T. W., Carlsson, T., de Andrade, A., Bruch, J., Höllerhage, M., Oertel, W. H. and Höglinger, G. U. (2014), Memory deficits correlate with tau and spine pathology in P301S MAPT transgenic mice. Neuropathology and Applied Neurobiology, 40: 833–843. doi: 10.1111/nan.12160
- Issue published online: 17 NOV 2014
- Article first published online: 17 NOV 2014
- Accepted manuscript online: 28 MAY 2014 12:26AM EST
- Manuscript Accepted: 21 MAY 2014
- Manuscript Received: 11 DEC 2013
- Deutsche Forschungsgemeinschaft. Grant Numbers: HO2402/6-1, HO2402/8-1
- German Ministry of Education and Research. Grant Number: BMBF GEF 10-54
- German Academic Exchange Service
- seventh Framework Programme. Grant Number: 220656
- dendritic spine;
- memory deficit;
- P301S transgenic mouse;
P301S MAPT transgenic mice (P301S mice) are a widely used model of frontotemporal dementia and parkinsonism linked to chromosome 17 with tau pathology (FTDP-17-tau). However, a systematic correlation between cognitive deficits and cellular tau pathology at different ages is still missing. Therefore, our study investigated memory deficits of P301S mice in relation to pathological tau species and dendritic spine pathology throughout adulthood.
We analysed P301S mice behaviourally with the novel open field, rotarod, and Morris water maze tests to measure deficits in locomotion, balance and cognition, respectively; immunohistochemically with different tau antibodies for specific tau species; and with Golgi staining for dendritic spine pathology.
We confirmed the occurrence of locomotor deficits at an age of 5 months and newly report memory deficits from 2.5 months of age onwards. At this early age, MC1 and CP13, but not AT180 immunoreactivity, was prominent in the hippocampus of P301S mice. Neuronal cell loss in the hippocampus of P301S mice was not observed to occur till 6 months of age. However, there was a significant reduction in the density of dendritic spines from young adulthood onwards in hippocampal pyramidal neurones.
In P301S mice, memory deficits precede the onset of locomotor dysfunction and coincide with the appearance of conformationally changed, S202-phosphorylated tau and reduced spine density in the absence of neuronal cell loss in the hippocampus. Our finding provides insights into the toxic effects of different tau species in vivo and may facilitate the development of new therapies against neurodegenerative tauopathies.