Thomas E. Lane

Coronavirus disease 2019 (COVID‐19) has rapidly escalated into a global pandemic that primarily affects older and immunocompromised individuals due to underlying clinical conditions and suppressed immune responses. Furthermore, COVID‐19 patients exhibit a spectrum of neurological symptoms, indicating that COVID‐19 can affect the brain in a variety of manners. Many studies, past and recent, suggest a connection between viral infections and an increased risk of neurodegeneration, raising concerns about the neurological effects of COVID‐19 and the possibility that it may contribute to Alzheimer's disease (AD) onset or worsen already existing AD pathology through inflammatory processes given that both COVID‐19 and AD share pathological features and risk factors. This leads us to question whether COVID‐19 is a risk factor for AD and how these two conditions might influence each other. Considering the extensive reach of the COVID‐19 pandemic and the devastating impact of the ongoing AD pandemic, their combined effects could have significant public health consequences worldwide. image

Microglia are the primary resident myeloid cells of the brain responsible for maintaining homeostasis and protecting the central nervous system (CNS) from damage and infection. Monocytes and monocyte‐derived macrophages arising from the periphery have also been implicated in CNS pathologies, however, distinguishing between different myeloid cell populations in the CNS has been difficult. Here, we set out to develop a reliable histological marker that can assess distinct myeloid cell heterogeneity and functional contributions, particularly in the context of disease and/or neuroinflammation. scRNAseq from brains of mice infected with the neurotropic JHM strain of the mouse hepatitis virus (JHMV), a mouse coronavirus, revealed that Lgals3 is highly upregulated in monocyte and macrophage populations, but not in microglia. Subsequent immunostaining for galectin‐3 (encoded by Lgals3 ), also referred to as MAC2, highlighted the high expression levels of MAC2 protein in infiltrating myeloid cells in JHMV‐infected and bone marrow (BM) chimeric mice, in stark contrast to microglia, which expressed little to no staining in these models. Expression of MAC2 was found even 6–10 months following BM‐derived cell infiltration into the CNS. We also demonstrate that MAC2 is not a specific label for plaque‐associated microglia in the 5xFAD mouse model, but only appears in a distinct subset of these cells in the presence of JHMV infection or during aging. Our data suggest that MAC2 can serve as a reliable and long‐lasting histological marker for monocyte/macrophages in the brain, identifying an accessible approach to distinguishing resident microglia from infiltrating cells in the CNS under certain conditions.