Dr. Reich is an expert in the advanced Magnetic Resonance Imaging (MRI) methods used to study the function of brain barriers in living primates, including humans. His team has developed novel imaging methods to visualize the activity of border-related structures, including openings in the blood-brain barrier (BBB), meningeal inflammation, lymphatic vessels, and the choroid plexus in humans. Several of these methods have also been applied to marmosets, a small monkey species that shares many physiological and genetic similarities with humans and that is increasingly used in scientific research. Much of Dr. Reich’s prior work focused on how changes in brain barriers are linked to the inflammation caused by multiple sclerosis (MS). As part of the CureAlz Brain Entry and Exit consortium, he is applying his expertise toward exploring how aging and inflammation contribute to barrier dysfunction in Alzheimer’s disease (AD). Dr. Reich recently collaborated with Dr. Kipnis on a study that described ACE points in mice and used MRI to demonstrate that these gates also exist in human brains.
In this project, Dr. Reich is expanding on the discovery of ACE points and has proposed three aims. In the first aim, his lab is characterizing the structure and function of ACE points during normal aging in both sexes. This work lays the important groundwork for future studies in patients with AD. In the second aim, his team is validating and applying MRI methods in marmosets to determine whether, as hypothesized, they possess ACE points similar to those found in humans and mice; this determination will help validate them as robust models for translational studies. In the third aim, they are validating in humans and marmosets the MRI imaging results with gold-standard high-resolution imaging of structures and mapping of other cell features (‘omics) that can only be done in human tissue samples or post-mortem (autopsy) brains. This is the only proposal studying barrier functions in living humans and marmosets and is expected to provide valuable translational knowledge.
Over the first year, the Reich lab determined that healthy aging leads to increased leakiness in brain barriers, but whether this is a compensatory response or a sign of pathology remains unclear. One possibility is that the brain actively increases permeability as a protective mechanism—recognizing damage and opening the floodgates to clear harmful substances. Alternatively, barrier dysfunction could be a byproduct of aging-related pathology, making the brain more vulnerable. Ongoing studies in both humans and marmosets, combined with autopsy and surgical tissue analyses, aim to disentangle these possibilities. Moving forward, the lab will expand participant cohorts, refine imaging methods in marmosets, and enhance histological analysis of human ACE points to deepen our understanding of barrier function and its role in AD.
