Getting ahead of Alzheimer’s
Losing your sense of direction is one of the earliest and most distressing signs of advanced Alzheimer’s disease. Now, a new U-M study sheds light on a unique neuron that may hold the key to understanding why this happens.The retrosplenial cortex is a brain region that has long been linked to spatial orientation and is known to be impaired early on in people with Alzheimer’s disease. Researchers have now identified a unique neuron with an equally unique function in the retrosplenial cortex. They found that specialized neurons can encode an individual’s sense of direction at all times, regardless of whether the individual is sitting still or on the move.
“This cell type appears uniquely evolved to solve a basic survival problem: knowing where you are and which way you’re facing at all times — whether you’re sitting in your office or out for a run,” says Omar Ahmed, associate professor of psychology and senior author of the study, which is published in the journal Progress in Neurobiology.
The research, Ahmed noted, provides a mechanistic explanation for why animals can subconsciously compute and remember where they are in their environment. This trait is critical to survival: it allows animals to track where they are, where the escape exit is (in case a predator is looming, for example, or in case of fire), and immediately turn toward the exit and take the shortest escape route.
“These neurons look different, express different genes, and process information in different ways compared to all their neighboring neurons. One of these key differences relates to a brain chemical called acetylcholine that increases when we are paying attention or running,” Ahmed says.
Acetylcholine strongly activates other types of neurons and changes the way they encode information. However, the unique retrosplenial neurons do not respond to acetylcholine in this way. Instead, they can consistently track head rotation, helping to keep track of orientation at all times, regardless of what you are doing or how much attention you are paying, Ahmed says.
This discovery may help explain why patients with Alzheimer’s often become disoriented in familiar places. Ahmed’s team is studying how these neurons function in mouse models of Alzheimer’s disease in the lab and investigating changes in human brains affected by the disorder.
“People living with neurodegenerative conditions such as Alzheimer’s disease or Parkinson’s disease can struggle to find their way home, even in familiar surroundings,” he says. “By understanding these unique neurons in the retrosplenial cortex, we are working toward the goal of one day restoring or preserving this critical function.”
The study’s co-authors are Izabela Jedrasiak-Cape, Chloe Rybicki-Kler, Isla Brooks, Megha Ghosh, Ellen Brennan, Sameer Kailasa, Tyler Ekins and Alan Rupp.
The research was supported by the National Institutes of Health R34NS127101 (Ahmed); NIH R01MH129282 (Ahmed); NIH P50NS123067 (Ahmed); Alzheimer’s Association Grant AARG-NTF-21–846572 (Ahmed); NIH T32-DC000011 (Rybicki-Kler, Ekins); NIH T32- DA007268 (Ekins); NIH T32-NS076401 (Brennan, Rybicki-Kler); and National Science Foundation graduate fellowship (Brennan).
T.Michael Knack - 1972, 1975, 1976, 1978 (Ph.D.)
Congratulations on this great research being done by Michigan students and scientist. This is a wonderful breakthrough for people with Alzheimer’s or other dementias. I certainly hope that the Trump administration doesn’t cancel these grants through the national science foundation or other sources. This is a wonderful way to spend taxpayer money on something that will benefit everyone! Keep up the good work! And Go Blue!
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Michael Wolk - 1970 BS
Does this discovery have wider ramifications in finding a cure for Alzheimer’s? I did find that the orientation issue as a marker for the disease helpful to know. Although it was unclear what benefit this might lead to.
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Marilyn Vineyard - 1974
Thank you for this updated information – in the last 2 years I have known two people who had both Parkinson’s and Alzheimer’s diseases plus Lewy body dementia which contributed to their deaths. One donated his brain to the U of M brain foundation for research. It is very important work.
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Gerard Jendras - 1991
Findings like this make me even more happy that I’ve volunteered to participate in multiple research projects involving transcranial stimulation this year. Hours spent within MRI scanners and wearing various kinds of headgear could well help others in the long run.
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Merton Shill - 1971; 1972; 1978
““Acetylcholine strongly activates other types of neurons and changes the way they encode information. However, the unique retrosplenial neurons do not respond to acetylcholine in this way. Instead, they can consistently track head rotation, helping to keep track of orientation at all times, regardless of what you are doing or how much attention you are paying, Ahmed says. This discovery may help explain why patients with Alzheimer’s often become disoriented in familiar places.” This summary seems to imply rather than state clearly that the retrosplenial neurons in Alzheimer’s do not respond to acetylcholine in the same way as they do in non-Alzheimer’s’ patients. I found this omission confusing. Or am I missing something?
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Youqi He
I agree with your point, because the title is “discover unique brain cell that may hold key to Alzheimer’s disorientation”, so this line should imply the same meaning that the retrosplenial neurons act differently in Alzheimer’s patients compared to non-Alzheimer’s patients.
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John Mullally - 1969
Comment that acetylcholine increases when running is very interesting as I have read many times that a semi rigorous workout helps to delay ( prevent? ) neurodegenerative diseases as it stimulates more of this good acectycholine in the brain. Keep exercising!!
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