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‘Ground Zero’ Brain Region for Alzheimer’s Highlighted

Essential for maintaining cognitive function as a person ages, the tiny locus coeruleus region of the brain is vulnerable to toxins and infection.

A critical but vulnerable region in the brain appears to be the first place affected by late onset Alzheimer’s disease and may be more important for maintaining cognitive function in later life than previously appreciated, according to a new review of the scientific literature.

The locus coeruleus is a small, bluish part of the brainstem that releases norepinephrine, the neurotransmitter responsible for regulating heart rate, attention, memory, and cognition. Its cells, or neurons, send branch-like axons throughout much of the brain and help regulate blood vessel activity. Its high interconnectedness may make it more susceptible to the effects of toxins and infections compared to other brain regions, said lead author Mara Mather.

Mather, Professor of Gerontology and Psychology at the University of Southern California Leonard Davis School of Gerontology, added that the locus coeruleus is the first brain region to show tau pathology, the slow-spreading tangles of protein that can later become telltale signs of Alzheimer’s disease. Though not everyone will get Alzheimer’s, autopsy results indicate that most people have some initial indications of tau pathology in the locus coeruleus by early adulthood, she added.

The norepinephrine released from the locus coeruleus may contribute to preventing Alzheimer’s symptoms. Studies conducted with rats and mice have shown that norepinephrine helps protect neurons from factors that kill the cells and accelerate Alzheimer’s disease, such as inflammation and excessive stimulation from other neurotransmitters.

Norepinephrine is released when someone is engaged in or mentally challenged by an activity, whether it’s solving problems in the workplace, completing a word puzzle, or playing a difficult piece of music.

Illustration showing a cut away of the brain with the locus coeruleus highlighted in blue.

Blue indicates the location of the locus coeruleus region in the brainstem. Image is credited to shutterstock.com/Tefi and is adapted from the USC press release.

“Education and engaging careers produce late-life ‘cognitive reserve,’ or effective brain performance, despite encroaching pathology,” Mather said. “Activation of the locus coeruleus-norepinephrine system by novelty and mental challenge throughout one’s life may contribute to cognitive reserve.”

About this Alzheimer’s disease research

Funding: This study was funded by National Institutes of Health grant RO1AG025340. The study was co-authored by Professor Emeritus Carolyn W. Harley of the Memorial University of Newfoundland.

Source: Beth Newcomb – USC
Image Credit: The image is credited to shutterstock.com/Tefi and is adapted from the USC press release.
Original Research: Abstract for “The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain” by Mara Mather and Carolyn W. Harley in Trends in Cognitive Sciences. Published online February 2016 doi:10.1016/j.tics.2016.01.001


Abstract

The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain

Research on cognitive aging has focused on how decline in various cortical and hippocampal regions influence cognition. However, brainstem regions play essential modulatory roles, and new evidence suggests that, among these, the integrity of the locus coeruleus (LC)–norepinephrine (NE) system plays a key role in determining late-life cognitive abilities. The LC is especially vulnerable to toxins and infection and is often the first place Alzheimer’s-related pathology appears, with most people showing at least some tau pathology by their mid-20s. On the other hand, NE released from the LC during arousing, mentally challenging, or novel situations helps to protect neurons from damage, which may help to explain how education and engaging careers prevent cognitive decline in later years.

Trends
In late life, lower LC neural density is associated with cognitive decline.

Because of the long unmyelinated axons of its neurons, high exposure to blood flow, and location adjacent to the 4th ventricle, the LC is especially vulnerable to toxins.

The tau pathology precursor of Alzheimer’s disease emerges in the LC by early adulthood in most people. However, the pathology typically spreads slowly, and only some end up with clinically evident Alzheimer’s disease.

Norepinephrine helps to protect neurons from factors that accelerate Alzheimer’s disease, such as inflammation and excitotoxicity.

Education and engaging careers produce late-life ‘cognitive reserve’ or effective brain performance despite encroaching pathology. Activation of the LC–NE system by novelty and mental challenge throughout life may contribute to cognitive reserve.

“The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain” by Mara Mather and Carolyn W. Harley in Trends in Cognitive Sciences. Published online February 2016 doi:10.1016/j.tics.2016.01.001

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