Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFNα production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.

Background: The neutrophil-tolymphocyte ratio (NLR) in peripheral blood is a wellestablished inflammatory marker, but its role in Parkinson's disease (PD) remains unclear. Objectives: To determine whether a different peripheral immune profile and NLR were present in PD patients. Methods: We conducted a case-control study that included 377 PD patients and 355 healthy controls (HCs). Leukocytes, subpopulations, and the NLR were measured. Multivariate linear regression analyses were applied to determine the differences between groups and the association between NLR and clinical characteristics in PD. A meta-analysis was performed to clarify the association between NLR and PD. Results: In our case-control study, the NLR was significantly higher in PD patients compared with HCs (2.47 AE 1.1 vs. 1.98 AE 0.91, P < 0.001). No association between NLR and age at onset, disease severity, or disease duration was found. The meta-analysis showed that the NLR was likely to be higher in PD patients. Conclusions: PD patients had an altered peripheral immune profile and a higher NLR compared with HCs.