Complement receptor 1 is expressed on brain cells and in the human brain

Genome wide association studies (GWAS) have highlighted the importance of the complement cascade in pathogenesis of Alzheimer's disease (AD). Complement receptor 1 (CR1; CD35) is among the top GWAS hits. The long variant of CR1 is associated with increased risk for AD; however, roles of CR1 in brain health and disease are poorly understood. A critical confounder is that brain expression of CR1 is controversial; failure to demonstrate brain expression has provoked the suggestion that peripherally expressed CR1 influences AD risk. We took a multi‐pronged approach to establish whether CR1 is expressed in brain. Expression of CR1 at the protein and mRNA level was assessed in human microglial lines, induced pluripotent stem cell (iPSC)‐derived microglia from two sources and brain tissue from AD and control donors. CR1 protein was detected in microglial lines and iPSC‐derived microglia expressing different CR1 variants when immunostained with a validated panel of CR1‐specific antibodies; cell extracts were positive for CR1 protein and mRNA. CR1 protein was detected in control and AD brains, co‐localizing with astrocytes and microglia, and expression was significantly increased in AD compared to controls. CR1 mRNA expression was detected in all AD and control brain samples tested; expression was significantly increased in AD. The data unequivocally demonstrate that the CR1 transcript and protein are expressed in human microglia ex vivo and on microglia and astrocytes in situ in the human brain; the findings support the hypothesis that CR1 variants affect AD risk by directly impacting glial functions

The effects of controlled sheep grazing on the dynamics of upland Agrostis-Festuca grassland

1. Agrostis capillaris-Festuca ovina-dominated communities are widespread in the uplands of Great Britain. They are agriculturally productive but little is known about how to manage this community for specific goals. Vegetation trajectories were examined in this plant community under different sheep grazing management regimes at two sites in Scotland. One site had a substantial presence of moorland species, the other was characterized by a more productive vegetation. Management consisted of maintaining sward heights of 3, 4.5 or 6 cm during the growing season, or complete exclusion of grazing stock.\ud \ud 2. Changes in species composition were small over the 7 years of the experiment. Few species invaded or were lost during the course of the study. The observed changes were largely as a result of shifts in abundance of the dominant species.\ud \ud 3. Maintenance of sward height at low levels (3 or 4.5 cm) during the growing season resulted in the spread of Nardus stricta where present. Where N. stricta was absent, the sward developed a higher content of mosses, specifically Hypnum jutlandicum and Rhytidiadelphus squarrosus.\ud \ud 4. Removal of grazing resulted in an increase of cover of grazing-intolerant species, such as Deschampsia flexuosa and Molinia caerulea, and in the cover of dwarf shrub species where present.\ud \ud 5. The two sites differed in the treatment that resulted in the smallest change in species composition. At the more productive site, maintenance of the sward at 4.5 cm resulted in the smallest overall change in species composition. At the less productive site, grazing the sward to 6 cm resulted in the smallest shift in vegetation composition. Grazing at this height appeared to prevent the spread of both M. caerulea and N. stricta.\ud \ud 6. The study demonstrates that sustainable grazing regimes for upland Agrostis-Festuca grasslands need to take into account both the initial composition of the vegetation, specifically the presence of species capable of replacing A. capillaris and F. ovina and of achieving dominance, and the overall productivity of the site

Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology

Funding Information: We thank Michel Goedert for the MAPTP301S mouse and Nathaniel Heintz for the Aldh1l1_eGFP-RPL10a mouse. This work was funded by the UK Dementia Research Institute (G.E.H., S.C.) which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK, the European Research Council (ERC) under the EU’s Horizon 2020 research and innovation programme (Grant No. 681181, T.S.J.) and grant NIH P50 AG033514 (Project 1, J.A.J.).Peer reviewedPublisher PD