Brain’s ‘blue dot’ may help identify Alzheimer’s disease earlier

The locus coeruleus (LC) is a tiny region of the brain that plays a disproportionate role in the functioning of our central nervous system. The name of LC comes from Latin for blue spot, its notable color is the product of intense chemical activity. This activity produces the main brain source of the vital neurotransmitter norepinephrine, which controls our “fight or flight” response to environmental stimuli and plays a role in our sleep-wake cycle and emotional regulation.

A new study, published in
Science Translational Medicinesuggests that changes in CL may provide a new way to indicate the early spread of Alzheimer’s disease in the brain.

The study was published by a collaborative group of researchers including
Dr Heidi Jacobs, assistant professor at the Gordon Center for Medical Imaging at Massachusetts General Hospital. The first author Jacobs spoke to Technological networks on the difficulties of studying this region. “It’s very deep in the brain, located in the bridge. This is a very difficult region to image with standard magnetic resonance imaging (MRI) tools because it is so faint. In the scanner, the coils that pass above your head end up just below the bridges, so the signal you capture becomes noisy.

“It’s also very small, about 2mm thick and 12mm long. Standard MRI methods have a resolution of 1 or 2 mm, so it’s difficult to capture, ”says Jacobs.

Could we make Alzheimer’s diagnoses decades earlier?

Alzheimer’s disease, the most common cause of dementia, is believed to be fueled by the spread of two pathological proteins: beta-amyloid (Aβ) and the microtubule-associated protein tau. The characteristic impairment that Alzheimer’s disease causes in memory and learning is believed to be the result of its impact on higher learning regions in the brain, such as the hippocampus and cortex. So why is the LC, nestled in the lower regions of the brainstem, a region of interest?

“What’s so interesting about this structure specifically in Alzheimer’s disease,” explains Jacobs, “is that it’s one of the first areas of the brain that accumulates tau pathology, potentially 30 to 40 years old. before seeing any of the clinical symptoms of Alzheimer’s disease. disease, even before seeing cortical damage. Being able to study this structure at an earlier age would potentially help us improve the early detection of Alzheimer’s disease.

To overcome the challenges of studying LC, Jacobs and his team used new advances in MRI – imaging at an improved resolution of 0.3 mm. As we age, the intensity of the MRI signal in the LC increases, as the activity of the region produces endogenous toxins which are then stored in measurable pigmented cells. However, it is believed that the early onset of tau buildup damages these pigmented cells, resulting in an altered signal that could be detected by the team’s ultra-sensitive MRI.

A sagittal slice of the brain (viewed from the side of the head) reveals the locus coeruleus, shown in blue. Credit: Heidi Jacobs

In their study, Jacobs’ team used a wide range of data. 221 Harvard Brain Aging Study (HABS) patients were recruited for MRI imaging and two postmortem data sets – 1,524 Religious Orders Study and Rush Memory and Aging Project (ROSMAP) case records and 2,145 cases from the National Alzheimer’s Coordinating Center (NACC) – have also been used. These latter data had previously been evaluated for the level of LC damage and Alzheimer’s pathology in the upper brain regions.

Functional results

Jacobs’ team showed that reductions in LC integrity were a key indicator of higher levels of tau protein accumulation in the entorhinal cortex. Increases in tau neurofibrillary tangles in the LC were associated with a poorer assessment of cortical pathology, referred to as Braak’s stage, while reduction in LC pigmentation was associated with later Braak stages.

It is important to note that, according to Jacobs, the disease processes most closely related to CL were those in the early stages of Alzheimer’s disease, a sign that the assessment of CL could be used as a predictor of the further spread of CL. disease.

A latest experiment has shown that reduced LC integrity is associated with faster decline in memory and executive function – key symptoms of Alzheimer’s disease.

“What we have shown is that the integrity of the LC is associated with these initial cortical patterns of tau pathology and cognitive decline,” explains Jacobs. She explains that some researchers thought the changes in LC were simply indicators of healthy aging, but the new findings show that the MRI signal may instead be an early biomarker for Alzheimer’s disease.

By providing an indication of disease risk decades before symptoms appear, the LC signal, Jacobs hopes, could enable more successful clinical trials where early intervention is seen as crucial for success. “We need to go sooner, and I think that’s where the clinical implication of this work lies,” Jacobs concludes.

About Hector Hedgepeth

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