Found in the Finnish population, a rare variant of the TYROBP gene significantly increases the risk of Alzheimer’s disease, a new study led by the University of Eastern Finland shows. This gene variant affects the function of microglia, the cells which regulate inflammation in the brain. The findings further confirm the role of altered inflammatory response and protein stress response in the early stages of Alzheimer’s disease.

A new study in mice reveals how cells called pericytes fine-tune blood pressure in the brain’s smallest capillaries. The findings show that a channel protein named TRPC3 plays a central role in this process and hints that the protein might offer a treatment target in disorders that involve disruptions in blood flow through cerebral vessels. The brain has countless blood vessels to fuel its large energy demands, including both larger arteries and arterioles and tiny capillaries. The body tightly controls the flow of blood through these cerebral vessels to keep brain tissue healthy and will dynamically respond to changes in blood pressure by relaxing or constricting vessels. In smaller capillaries in some parts of the body, pericytes wrap around the capillaries and adjust blood flow by either relaxing or constricting to change the capillaries’ diameters. In this study, Hannah Ferris and colleagues leveraged microscopy and other techniques to understand whether and exactly how pericytes constrict to regulate blood flow into the brain’s tiniest capillaries in mice. They observed that pericytes quickly responded to rising blood pressure by constricting and decreasing the diameter of transitional blood vessel segments that link arterioles and capillaries. Further research tied this constriction to the activation of TRPC3 and of calcium channels, which acted sequentially to flood pericytes with calcium ions and caused them to contract. The scientists also found that ablating the TRPC3 gene prevented pericytes from properly contracting in response to pressure but did not affect blood pressure regulation in larger arterioles. “This discovery provides a framework for advancing the understanding of cerebral hemodynamic regulation and prompts reconsidering pericytes and TRPC3 channels as therapeutic targets in cerebrovascular disorders, including cerebral small vessel disease and Alzheimer’s disease,” Scott Earley writes in a related Focus.

The Hinda and Arthur Marcus Institute for Aging Research, which researches solutions to the most pressing challenges of aging, including Alzheimer’s disease, dementia, osteoporosis, falls, and frailty, has promoted Dae Hyun Kim, MD, MPH, ScD, to the newly created position of associate director. He has been a researcher at the Marcus Institute since 2018.

A harmful form of the tau protein, which builds up in Alzheimer’s disease and similar brain disorders, can directly damage blood vessels in the brain, according to a new study by researchers at the Lewis Katz School of Medicine at Temple University. It does this by changing how the cells lining the blood vessels produce energy, which leads to inflammation and makes the blood-brain barrier – the brain's protective shield – weaker.

The discovery, reported online in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association, uncovers a novel molecular mechanism that potentially explains tau-mediated vascular dysfunction in the brain and highlights the importance of focusing on early neurovascular changes mediated by tau to help prevent or slow down damage to the blood-brain barrier in Alzheimer’s disease.

Exposure to air pollution derived ultrafine particles alters gene transcription by epigenetic mechanisms, a new study shows. The changes affected, for example, cellular survival.