Magnetic resonance elastography (MRE) [1] is capable of measuring the mechanical properties of the in vivo mouse brain [2,3]. Recent findings demonstrated that tissue mechanical properties are sensitive to neurogenesis in the hippocampus of the mouse due to enriched environment [4] and Parkinson's disease model [5]. Here we investigate early effects of Alzheimer's disease (AD) under consideration of environmental conditions.30 C57/B6 mice were separated into two groups with different environment conditions: standard cage (standard environment, SE: n=15) and cage with frequently rearranged interior design (enriched environment, EE: n=15) which is a robust stimulus for adult neurogenesis in the dentate gyrus [5,6]. The two groups were investigated by MRE at 6 weeks(6w), 3 months(3m) and 6 months(6m) of age (n=5 per age group). In AD, a total of n=54 APP23 mouse with C57BL/6 background were investigated, (SE/EE: n=6/5, 9/15 and 11/8 at 6w, 3m and 6m). MRE was performed on a 7T scanner (Bruker PharmaScan, Germany). 900Hz external mechanical vibration was induced by an air-cooled Lorentz coil and recorded by a gradient echo sequence with motion sensitizing gradients(MSG) [3]. Four axial slices with slice thickness of 1mm were acquired. Further imaging parameters were: 128x128 matrix, 25 mm FoV, 14.3 ms TE, 116.2 ms TR, 285 mT/m MSG strength, 8 time steps over a vibration period. A 2D-Helmholtz inversion was performed, yielding the storage modulus G' and the loss modulus G″ reflecting the tissue's elasticity and viscosity, respectively. Parameters were averaged within regions-of-interest (ROI) including the hippocampus (index h) and full brain without hippocampus (rest of brain, index rb). ROI selection, example wave image and elastogram are shown in Fig.1.In controls, we observed the hippocampus to be more elastic and less viscous than the rest of brain in SE (G'_h = 7.6±0.8 kPa vs. G'_rb=6.4±0.9 kPa, P < 0.001; G″_h = 1.3±0.3 kPa vs. G″_rb=1.7±0.2 kPa, P = 0.005), however, in EE, the difference was only observed in G' (G'_h = 7.5±0.9 kPa vs. G'_rb=6.0±1.0 kPa, P < 0.001) (Fig.2) [5]. Within 6 weeks, no effect of AD was seen in G'_h, G'_rb, and G''_rb. Henceforth, we focused on G″_ratio=G″_h/G″_rb as a measure of the relative decrease in hippocampal viscosity. Considering the effect of environment in healthy controls, G″_ratio was not changed in SC but increased in EE between 6w and 6m (p<0.05)(Fig.3). In AD, no significant changes were observed with SE. However, a significant decrease of G″_ratio was found between 6w and 6m in EE (p<0.01) (Fig.4). Pooling SE-data gave no significant AD effect while in EE, G″_ratio was lower in AD at 3m (p= 0.02) and 6m (p= 0.002) (Fig. 5).Our results provide evidence that the hippocampus is different from the rest of the brain, both in elasticity and viscosity. Furthermore, viscosity seems to be more sensitive to environmental effects as revealed by the increase of G''_h in healthy mice exposed to EE. It is known that EE stimulates neuronal proliferation in the hippocampus of the mouse[6,7]. Furthermore, it is expected that elasticity increases when neurons are integrated into the mechanical matrix of the brain. As we did not observe an increase in G' due to EE we assume that newborn neurons are incompletely integrated which yields a higher portion of mobile elements in the tissue matrix. Since mobile elements influence mainly the loss properties of tissue, an increased G''-modulus is expected upon higher cell density. In AD, the normalized viscosity G″_ratio decreased whereas elasticity-related measures remained unchanged. This indicates reduction of the number of mobile elements in the mechanical tissue matrix which – in the light of neuronal proliferation stimulated by EE – might reflect degeneration of new neurons due to the disease. Since newborn neurons are enriched in EE-mice, the effect of AD was more apparent in this group as compared to SE-mice. More research is needed to correlate our MRE findings with number of neurons in the hippocampal regions. Altogether, our study adds information to the still unknown link between tissue mechanical properties and neuronal health in degenerative diseases and complements previous work on AD in the mouse at later time points[8].