Promoting diversity and overcoming publication barriers in Latin American neuroscience and Alzheimer's disease research : a call to action

Alzheimer's disease (AD) is a global health issue. Because AD is a condition demanding effective management, its socioeconomic burden is immense and threatens the health systems of both low- and middle-income (LMIC) and high-income (HIC) countries. However, while most of the HICs are increasing their budget for AD research, the situation is different in LMICs, and resources are scarce. In addition, LMIC researchers face significant barriers to publishing in international peer reviewed journals, including funding constraints; language barriers; and in many cases, high article processing charges. In this perspective, we discuss these disparities and propose some actions that could help promote diversity, and ultimately translate into improved AD research capacity in LMICs, especially in Latin American and Caribbean countries

Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon’s role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid β burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid β burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid β secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid β homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid β secretion, defining a new way to target AD and other similar diseases therapeutically