Basic Science and Pathogenesis.

Background: Angiotensin-converting enzyme (ACE) is a validated risk locus for developing late-onset Alzheimer's disease (LOAD). ACE1 controls blood pressure through the renin-angiotensin system (RAS), but it is also present and acts locally in the brain. Hypertension is associated with an increased risk for developing AD, and people taking select RAS-targeting therapeutics have reduced incidence of AD.

Epigenetic dysregulation in Alzheimer's disease peripheral immunity.

The peripheral immune system in Alzheimer's disease (AD) has not been thoroughly studied with modern sequencing methods. To investigate epigenetic and transcriptional alterations to the AD peripheral immune system, we used single-cell sequencing strategies, including assay for transposase-accessible chromatin and RNA sequencing. We reveal a striking amount of open chromatin in peripheral immune cells in AD.

Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment.

Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity is altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on CSF from 45 cognitively normal subjects ranging from 54 to 82 years old.

Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress.

Stem cells in stratified epithelia are generally believed to adhere to a non-hierarchical single-progenitor model. Using lineage tracing and genetic label-retention assays, we show that the hard palatal epithelium of the oral cavity is unique in displaying marked proliferative heterogeneity. We identify a previously uncharacterized, infrequently-dividing stem cell population that resides within a candidate niche, the junctional zone (JZ).