Molecules of senescent glial cells differentiate Alzheimer's disease from ageing

BACKGROUND: Ageing is a major risk factor for Alzheimer's disease (AD), which is accompanied by cellular senescence and thousands of transcriptional changes in the brain. OBJECTIVES: To identify the biomarkers in the cerebrospinal fluid (CSF) that could help differentiate healthy ageing from neurodegenerative processes. METHODS: Cellular senescence and ageing-related biomarkers were assessed in primary astrocytes and postmortem brains by immunoblotting and immunohistochemistry. The biomarkers were measured in CSF samples from the China Ageing and Neurodegenerative Disorder Initiative cohort using Elisa and the multiplex Luminex platform. RESULTS: The cyclin-dependent kinase inhibitors p16/p21-positive senescent cells in human postmortem brains were predominantly astrocytes and oligodendrocyte lineage cells, which accumulated in AD brains. CCL2, YKL-40, HGF, MIF, S100B, TSP2, LCN2 and serpinA3 are biomarkers closely related to human glial senescence. Moreover, we discovered that most of these molecules, which were upregulated in senescent glial cells, were significantly elevated in the AD brain. Notably, CSF YKL-40 (β=0.5412, p<0.0001) levels were markedly elevated with age in healthy older individuals, whereas HGF (β=0.2732, p=0.0001), MIF (β=0.33714, p=0.0017) and TSP2 (β=0.1996, p=0.0297) levels were more susceptible to age in older individuals with AD pathology. We revealed that YKL-40, TSP2 and serpinA3 were useful biomarkers for discriminating patients with AD from CN individuals and non-AD patients. DISCUSSION: Our findings demonstrated the different patterns of CSF biomarkers related to senescent glial cells between normal ageing and AD, implicating these biomarkers could identify the road node in healthy path off to neurodegeneration and improve the accuracy of clinical AD diagnosis, which would help promote healthy ageing

Phytoplankton community response to episodic wet and dry aerosol deposition in the subtropical North Atlantic

Atmospheric aerosol deposition into the low latitude oligotrophic ocean is an important source of new nutrients for primary production. However, the resultant phytoplankton responses to aerosol deposition events, both in magnitude and changes in community composition, are poorly constrained. Here, we investigated this with 19 d of field and satellite observations for a site in the subtropical North Atlantic. During the observation period, surface dissolved aluminum concentrations alongside satellite-derived aerosol and precipitation data demonstrated the occurrence of both a dry deposition event associated with a dust storm and a wet deposition event associated with strong rainfall. The dry deposition event did not lead to any observable phytoplankton response, whereas the wet deposition event led to an approximate doubling of chlorophyll a, with Prochlorococcus becoming more dominant at the expense of Synechococcus. Bioassay experiments showed that phytoplankton were nitrogen limited, suggesting that the wet deposition event likely provided substantial aerosol-derived nitrogen, thereby alleviating the prevalent nutrient limitation and leading to the rapid observed phytoplankton response. These findings highlight the important role of wet deposition in driving rapid responses in both ocean productivity and phytoplankton community composition