At first glance, the myelin sheath is fairly unassuming. This fatty insulating layer surrounds nerve fibers, serving as both a protective membrane and a facilitator, allowing electrical impulses to travel efficiently along the nerve cells. But damage to the myelin sheath — and the resulting axonal dysfunction — can have catastrophic consequences, forcing nerve impulses to slow or even stop. This can disrupt everyday function, causing blurred vision, cognitive changes, and motor challenges.
Neurological conditions like multiple sclerosis (MS) and Alzheimer’s disease (AD) are among the most common causes of myelin damage, making myelin and its components intriguing prospects for neurological research. Yale researchers recently conducted a study to better understand the link between AD and myelin sheath damage. Read on to explore the team’s findings, which could be used to understand the onset of the disease.
5XFAD Mice and Human AD Brains Used in Myelin Sheath Research
Myelin is produced by oligodendrocytes, which are glial cells within the nervous system. Past research shows that oligodendrocytes are particularly vulnerable to AD, making these cells interesting candidates for AD research. While experts acknowledge that disruptions in myelin and axonal structures occur in AD, the underlying mechanisms behind these disruptions are unclear. This is where the Yale team decided to dig in, analyzing myelin in two types of brains: postmortem human brains from AD donors and the brains of 15-month-old male and female 5XFAD mice. The latter are widely used AD models and feature early amyloid-beta plaque deposition and notable cognitive decline.
Evaluating Proteins Within the Myelin Sheath
The Yale researchers focused on proteins found in the sub-compartment that lies between an axon and its myelin sheath. The team started by tagging applicable proteins with a special antibody, which enabled the researchers to isolate and inspect the proteins of the above-mentioned sub-compartment. The results were unsurprising: The researchers noted protein differences between tissue affected by AD and brain tissue from healthy subjects, including “structural abnormalities at the myelin-axon interface that may hinder electrical signaling.”
Amyloid Build-Up Near Paranodes Provides Clues to Axon Dysfunction
The Yale research refers to “paranodes,” which are tiny regions where the myelin sticks directly to the nerve to anchor it in place for speedy signaling. Interestingly, the team noted several changes in the proteins at these paranodes when evaluating AD brains. The team discovered that amyloid can build up in unique spirals near the paranodes, impairing the function of myelin and “clogging up” axon channels, impacting nerve function. The researchers even observed some swelling of the axon near these amyloid spirals, which principal investigator Jaime Grutzendler compared to “tying a knot around a straw.” Could this data help the team improve these myelin-axon abnormalities? Grutzendler says the team is “still at the hypothesis-generating phase.” However, the implications for future research are promising.
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The team has only just begun. In the future, they hope to wield the newfound protein data to provide insights into the early development of AD. “If we learn how the proteins that make up the myelin sheath are affected in the diseased state compared to a non-diseased state, we might be able to figure out what’s going on when the disease develops,” says Grutzendler.
Scantox Neuro offers in vivo research with 5xFAD mice and related behavioral, biochemical, and histological analysis methods. Several in vitro models to study AD are also available and can be adjusted to fit your needs. Additionally, we offer several classical multiple sclerosis in vivo models to evaluate de- and remyelination.
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