CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio

Mental Health and Mental Wellbeing of Black Students at UK Universities: A Review and Thematic Synthesis

BACKGROUND: There is a knowledge gap about the experiences that affect the mental health of Black university students in the UK. Current research is focused on understanding the continuation, attainment and progression gap between Black students and non-Black students. It is essential to know more about the interactions between personal and institutional factors on the mental health of Black students to explain the inequalities in their experiences and outcomes across the university lifecycle. The current study set out to thematically synthesise articles that explore the experiences that affect the mental health and mental well-being of Black university students in the UK. METHODS: This study is a qualitative thematic synthesis of a literature review. We developed search strategies for four online databases (PubMed, Social Science Premium Collection via ProQuest, Open Access Theses and Dissertations, and Open Grey) covering January 2010 to July 2020. This search was combined with a manual search of reference lists and related citations. All articles in English addressing mental health and mental well-being experiences among Black university students studying at a UK university were included. Critical Appraisal Skills Programme Checklist was used to assess bias. A thematic synthesis was conducted using Braun and Clarke (2006)’s six-step guide to develop descriptive themes and analytical constructs. RESULTS: Twelve articles were included. Several themes were identified as affecting the mental health of Black university students in the UK: academic pressure, learning environment, Black gendered experience, isolation and alienation, culture shock, racism and support. DISCUSSION: This review provides an appraisal of the factors affecting the mental health and mental well-being of Black students at UK universities, which need to be addressed by higher education policy-makers and key decision-makers. Further research is needed about the mental health experiences of Black university students in relation to Black identities, suicidality, mental health language, the physical environment, and racism and other institutional factors

A Qualitative Evaluation of the Motivations, Experiences, and Impact of a Mental Wellbeing Peer Support Group for Black University Students in England and Wales: The Case of Black Students Talk

Online peer support programs could address mental wellbeing concerns reported by Black students. The current evaluation explored Black university students’ motivations, experiences, and perceived impacts of an online mental wellbeing peer support group (Black Students Talk [BST]) in England and Wales. We conducted two focus groups with Black Students Talk attendees and one with facilitators. Data were analyzed using inductive thematic analysis. Three main themes and eight sub-themes where identified related to (i) Motivation: Impact of racism on mental wellbeing; (ii) Experience: The Black Students Talk experience; and (iii) Impact: Mental wellbeing outcomes. Benefits of Black Students Talk for Black students included advice, rest, validation, and support in the context of their race and experiences of racism. Facilitators had a unique sub-theme concerning their training and support. While racism exists at universities, online peer support can offer valuable benefits for Black students’ mental wellbeing, social connectedness, and Black-only networks. Programs need to be co-created and delivered by trained Black students who receive reflective practice with a Black practitioner. Further independent evaluations using insights from survey and interview data are needed