Olaleye, Olajide E

ABSTRACT Imaging mass spectrometry has made significant advancements in recent years owing to its ability to study the spatial localization and abundance of proteins, peptides, lipids, glycans, metabolites, and drugs. In this study, we employed an imaging mass spectrometry‐based workflow called MALDI‐IHC, which uses antibodies conjugated with photocleavable mass‐tags, to investigate the detection of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) along with pan‐cytokeratin in formalin‐fixed paraffin‐embedded (FFPE) sections from cases with breast cancer. The expression of ER, PR, and HER2 was consistent with the clinical diagnosis based on conventional immunohistochemistry, lacking signal in triple‐negative cases and concordant signals in the cases that were classified as ER+/PR+/HER2+, ER+/PR+/HER2−, and ER−/PR−/HER2+ groups, respectively. In addition, the potential utility of a seconday antibody‐based MALDI‐IHC approach for HER2 expression was evaluated. In agreement with immunohistochemistry results, HER2 expression co‐localized within tumor regions in a HER2+ breast cancer case, while no expression was observed in a HER2− case. Collectively, these results highlight the potential of imaging mass spectrometry‐based MALDI‐IHC workflow for multiplexed detection of proteins in clinically relevant tissue sections.

Abstract Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data‐driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer's or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti‐inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritizing candidates and exploring underlying mechanisms. Highlights We present a systematic review of studies reporting association between drugs prescribed for other conditions and risk of dementia including 139 million people and 1 million cases of dementia. Our work supports some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment. Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue. Our work should help prioritize drugs for entry into adaptive platform trials in Alzheimer's disease and will serve as a useful resource for those investigating drugs or classes of drugs and risk of dementia.