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BackgroundAlzheimer’s disease (AD) causes progressive loss of memory and cognition, exacerbated by APOE4, the greatest genetic risk factor for AD. One proposed mechanism for apolipoprotein E (apoE) effects on cognition is via NMDAR-dependent signaling. APOE genotype-specific effects on this pathway were dissected using EFAD-transgenic (Tg) mice (5xFAD mice, that over-express human amyloid-beta (Aβ) via 5 familial-AD (FAD) mutations, and express human apoE), and 5xFAD/APOE-knockout (KO) mice. Previous data from EFAD-Tg mice demonstrate age-dependent (2-6 months), apoE-specific effects on the development of Aβ pathology. This study tests the hypothesis that apoE4 impairs cognition via modulation of NMDAR-dependent signaling, specifically via a loss of function by comparison of E4FAD mice with 5xFAD/APOE-KO mice, E3FAD and E2FAD mice.ResultsUsing female E2FAD, E3FAD, E4FAD and 5xFAD/APOE-KO mice aged 2-, 4-, and 6-months, the Y-maze and Morris water maze behavioral tests were combined with synaptic protein levels as markers of synaptic viability. The results demonstrate a greater age-induced deficit in cognition and reduction in PSD95, drebrin and NMDAR subunits in the E4FAD and 5xFAD/APOE-KO mice compared with E2FAD and E3FAD mice, consistent with an apoE4 loss of function. Interestingly, for NMDAR-mediated signaling, the levels of p-CaMK-II followed this same apoE-specific pattern as cognition, while the levels of p-CREB and BDNF demonstrate an apoE4 toxic gain of function: E2FAD > E3FAD > 5xFAD/APOE-KO > E4FAD.ConclusionThese findings suggest that compared with E2FAD and E3FAD, E4FAD and 5xFAD/APOE-KO mice exhibit enhanced age-induced reductions in cognition and key synaptic proteins via down-regulation of an NMDAR signaling pathway, consistent with an apoE4 loss of function. However, levels of p-CREB and BDNF, signaling factors common to multiple pathways, suggest a gain of toxic function. Publications in this field present contradictory results as to whether APOE4 imparts a loss or gain of function. As with the results reported herein, the overall effect of APOE4 on a given CNS-specific measure will be the product of multiple overlapping mechanisms. Thus, caution remains critical in determining whether APOE gene inactivation or therapies that correct the loss of positive function related to apoE4, are the appropriate therapeutic response.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-015-0002-2) contains supplementary material, which is available to authorized users.

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Monoculture and improper management may reduce soil fertility and deteriorate soil structure in Black soils (Mollisols) of Northeast China. The experiment was carried out from 2015 to 2016 in Black Soils comprising five cropping systems: continuous corn (CC), soybean-corn rotation (SC), cornsoybean rotation (CS), fallow-corn (FC), and fallow-soybean (FS). Our results showed that CS and FS treatments significantly increased mean weight diameter (MWD) and fractal dimension (D) in mechanical stability aggregates (MSAs), and increased MWD and geometric mean diameter (GMD) in water-stable aggregates (WSAs) compared with CC treatment. These two treatments were also significantly increased water-stable aggregates stability rate (WSAR), but decreased percentage of aggregates destruction (PAD) than CC treatment. Meanwhile, CS and FS treatments exhibited a higher carbon accumulation than cc treatment in bulk soils. Soil organic carbon (Soc) concentration in WSA 0.106-0.25 ,WSA 2-5 mm and WSA 0.5-1 mm had a dominant effect on aggregate stability. Simutaneously, Soc in WSA >5 mm affected SOC concentration in bulk soils. As a whole, the CS and FS treatments can increase the percentage of macro-aggregates, enhance aggregate stability, as well as increase SOC concentration in bulk soils and all soil aggregate sizes. Soil organic carbon (SOC) plays a key role in forming and stabilizing soil structure, enhancing soil physical properties, and nutrient recycling 1-3. Soil aggregate, the basic unit of soil structure, mediates many physical and chemical processes in soils 4-8 , such as soil compaction, soil nutrient recycling, soil erosion, root penetration, and crop yield 9. Aggregate stability is frequently used as an indicator of soil structure 10-12 because better soil structure and higher aggregate stability are vital to improve soil fertility, soil sustainability, and productivity 13,14. SOC influenced aggregate stability and soil structure 15,16. The stability of organic carbon in different size aggregates is different. Organic carbon in the micro-aggregates is less susceptible to change than it is in the macro-aggregates 17. The soil organic matters of different cropping systems differed based on the quantity and quality of the crop residue coverage and the environment, affecting the organic carbon contents of the soil and the aggregate stability 18. The cropping systems mainly create conditions for the decomposition and transformation of soil organic matter by changing the distribution of soil organic carbon and the active habitat of microorganisms, thereby causing changes in soil aggregates 19. Soil mean weight diameter (MWD), geometric mean diameter (GMD), fractal dimension (D), percentage of aggregates destruction (PAD) and water-stable aggregates stability rate (WSAR) are all indicators of soil aggregate stability. The larger the MWD and GMD values are, the higher the average particle size agglomeration of soil aggregates are, and the stronger the stability of soil structure is 20. Castrignano and Stelluti 21 found that ...