Myelin acts as insulation for millions of brain cells, allowing for swift and efficient transmission of signals across brain regions. Despite its crucial role, little is known about how stable this structure is in the adult brain and what impact aging has on its maintenance. Yale neurologists Robert Hill, Alice Li, and Jaime Grutzendler devised techniques to track and precisely image myelin throughout the lifetime of the mouse. They discovered that myelin continues to form and restructure in the adult brain — indicating the potential for lifelong change. They also learned that during aging, myelin begins to deteriorate and myelin debris accumulate over time.
- May 28, 2016
New research bolsters the case that brain-derived microglia need TREM2 to essentially wall off amyloid plaques, but exactly how they do that remains up for debate. As reported in the May 18 Neuron, scientists led by Jaime Grutzendler at Yale University, New Haven, Connecticut, used confocal and super-resolution microscopy to show that TREM2-positive microglia surround and encase amyloid fibrils, protecting neurons in the process. Yet TREM2 itself appears to lend little support to phagocytosis of Aβ. The technical caliber of the work and the quality of the microscopy led researchers in the AD field to call the study “stunning.” It comes on the heels of another paper, in the April 18 Journal of Experimental Medicine, which suggests the microglia that surround plaques are brain-derived, not peripheral myeloid cells as others had suggested previously.
- May 18, 2016
In the battle against Alzheimer’s disease, inflammation may be an ally, not a foe, a new study has found. Immune cells in the brain previously blamed for Alzheimer’s actually protect against the disease by corralling the damage-causing amyloid plaques, according to the Yale University study, published Wednesday in the journal Neuron. The findings suggest that inflammation byproducts of these immune cells, known as microglia, probably don’t cause Alzheimer’s, nor are they as effective as previously believed at “gobbling up” the plaques, both of which have been hypothesized, said Jaime Grutzendler,associate professor of neurology and neuroscience and the study’s lead author. Rather, he said, the cells act as a physicalbarrier that encloses the spiky plaques, preventing outward expansion and making them less toxic. “They’re sort of like garbage compactors,” he said. “They tightly surround the plaques and make them inert and less damaging . . . by creating a capsule.”
- April 17, 2016
An amyloid plaque (in purple) is surrounded by branches of damaged neurons (multiple colors) in the brain of a mouse with Alzheimer’s disease. The mouse brain tissue was labeled with specific dyes that reveal damaged neurons and amyloid plaques, fixed and then sliced into 30-micron thick sections. The image was collected using a confocal microscope. The dystrophic axons were color-coded for depth in the Z-axis and the amyloid plaque was colored purple. The image is 60x60 microns and projected through 20 microns in depth.
- January 12, 2016
A long-term reduction in neuronal activity reduces amyloid plaques associated with Alzheimer’s disease, Yale University researchers have found. The study, using mouse models of Alzheimer’s, found the opposite is also true — triggering an increase in neuronal activity spurs creation of plaques and toxic amyloid beta peptides believed to trigger the disease.
- June 25, 2015
An investigation of blood flow network in the brain has revealed some surprising behavior of vessels during stroke, according to Yale researchers
- January 29, 2015
In Alzheimer’s disease (AD), β-amyloid plaques are tightly enveloped by microglia but the significance of this phenomenon is unknown. Here the authors used confocal and in vivo two-photon imaging in AD mouse models and revealed that microglia constitute a physical barrier that prevents the formation of neurotoxic hotspots of protofibrillar β-amyloid and shields adjacent neurons and synapses from the toxic effect of amyloid plaques
- May 30, 2014
Our recent paper in Nature Medicine was highlighted in Nature Methods
- April 01, 2014
New technique developed in the Grutzendler Lab
- March 06, 2014
Angiophagy Clears Clots in Microvessels