Lily Camp

Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain. We compare actively immunized patients with AD with nonimmunized patients with AD and neurologically healthy controls, identifying distinct microglial states associated with Aβ clearance. Using high-resolution spatial transcriptomics alongside single-cell RNA sequencing, we delve deeper into the transcriptional pathways involved in Aβ removal after lecanemab treatment. We uncover spatially distinct microglial responses that vary by brain region. Our analysis reveals upregulation of the triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) in microglia across immunization approaches, which correlate positively with antibody responses and Aβ removal. Furthermore, we show that complement signaling in brain myeloid cells contributes to Aβ clearance after immunization. These findings provide new insights into the transcriptional mechanisms orchestrating Aβ removal and shed light on the role of microglia in immune-mediated Aβ clearance. Importantly, our work uncovers potential molecular targets that could enhance Aβ-targeted immunotherapies, offering new avenues for developing more effective therapeutic strategies to combat AD.

BACKGROUND: Given the potential positive and negative impacts of cannabis use during cancer care, more information is needed to understand how changes in cannabis legalization and social norms have affected cannabis use and clinical disclosure among cancer survivors. OBJECTIVES: The purpose of this research was to explore cannabis behaviors, disclosure, and information needs among cancer survivors. METHODS: The study team conducted cross- sectional analyses using descriptive statistics to assess data collected via an online survey distributed through online health communities. FINDINGS: This analysis included 719 participants, and most reported currently undergoing treatment. About one-third reported current cannabis use. Cannabis use varied across the cancer care continuum, and most of those using cannabis discussed their use with a healthcare provider and reported interest in receiving more information about cannabis.

Background: Smell and Taste disorders (SATDs) are underreported. There is a wide range of aetiology but recently we have seen growing prevalence related to Covid-19 infection. SATDs have broad implications for people’s lives, including, a significant impact on nutritional intake and eating behaviours which we further explore here. Methods: This was a cross-sectional observational study using an online questionnaire to gather data. Questions covered aetiology of SATDs, impact on BMI, social eating habits and enjoyment of food. Results: A total of 794 participants responded of which 75% were female and the majority (46%) 56-70 years. Since the onset of their SATDs: 46% reported no change in weight, 24% weight gain, 15% weight loss, 52% felt it impacted how healthily they ate, 59% dined out less or not at all anymore, 59% no longer enjoy preparing food at home, 58% do not enjoy eating out and 54% do not enjoy eating at the homes of friends/ family/ partners. Conclusion: We have built on existing literature highlighting the impact SATDs have on participant eating behaviour. Although there is clearly an impact on diet and social behaviours around food/ eating it is hard to know the full health and economic impact. Especially when we consider that poor nutritional intake has been linked to cognitive decline in an older age group, it is an important area for further research and it may be beneficial for healthcare providers to offer tailored nutritional advice and discuss possible coping mechanisms upon diagnosis of SATDs.