HMN 2025: How Impaired touch perception in Alzheimer’s is associated with Tau pathology and lower cognitive scores

Alzheimer’s disease (AD) is a neurodegenerative condition characterized by the progressive deterioration of brain cells, which prompts memory loss, a decline in mental functions and behavioral changes. Estimates suggest that this disease affects approximately 1 in 14 people who are more than 65 years old and over 35% of people who are over 85 years old.

Due to its prevalence and debilitating nature, AD has become the focus of numerous neuroscience and medical studies. Most of these studies examined brain regions and neurogenetic processes that appear to be different in people diagnosed with AD.

Recently, some neuroscientists gathered evidence suggesting that parts of the brain that support somatosensory processing (i.e., the interpretation of tactile stimuli, pressure and the body’s position in space), are also affected in individuals with AD. Yet the extent to which these tactile sensation-related deficits play a role in the cognitive decline typical of AD has not yet been determined.

Researchers at Huazhong University of Science and Technology, the Chinese PLA medical academy and other institutes recently carried out a study involving both humans and genetically engineered mice, aimed at further exploring the link between changes in tactile processing and cognition in AD. Their findings, published in Nature Neuroscience, show that individuals with AD show detectable deficits in the perception of tactile stimuli and these deficits are correlated with cognitive impairments.

“Somatosensory processing has been shown to be correlated with brain development and cognitive function, but whether and how tactile sensory deficits affect cognition decline remains unclear,” Yang Zhou, Wen-Lian Li and their colleagues wrote in their paper. “We show that tactile function is impaired in individuals with AD, and this impairment is inversely correlated with Montreal Cognitive Assessment scores and positively correlated with Tau pathology.”

An overlooked feature of AD

To carry out their experiments, Zhou, Li and their colleagues recruited a group of patients with AD. They then tested both the tactile sensitivity of these people and their cognitive abilities, using established experimental tasks. They also performed experiments involving genetically engineered mice with three gene mutations associated with AD in humans.

In addition to probing sensory processing and cognitive skills, the researchers looked at the prevalence of the protein Tau. In AD, this protein is known to become abnormally shaped and accumulate inside neurons, disrupting their function and ultimately leading to their death.

Finally, they focused on a population of cells known as cholecystokinin (CCK)-expressing neurons. These neurons produce the signaling molecule CCK and contribute to the transmission of tactile information from the spinal cord to the brain.

Zhou, Li and their colleagues found that people diagnosed with AD exhibited significant deficits in the perception of tactile stimuli, which were associated with their cognitive abilities. Specifically, more significant tactile sensation-related deficits were linked with lower scores on a cognitive ability test.

“We observed similar deficits in presymptomatic 3×Tg AD mice and found that cholecystokinin (CCK)-expressing neurons in the spinal cord are highly vulnerable to Tau pathology,” wrote the authors.

Could restoring sensory functions improve cognition?

The researchers identified a population of CCK-expressing neurons in the mouse spinal cord that appeared to be most vulnerable to Tau pathology and were damaged early. They then explored how mutant Tau in these neurons or the silencing of Tau altered gene activity, as well as the animals’ ability to process tactile information and their mental functions.

“Expressing mutant Tau-P301S in spinal cord CCK-expressing neurons aberrantly activates the transcription factor c-Maf, inhibits CCK neurons and induces tactile deficits, whereas silencing Tau or c-Maf restores tactile sensation and improves cognition in AD model mice,” wrote Zhou, Li and their colleagues.

“Together, these gain- and loss-of-function studies demonstrate that Tau pathology in spinal cord CCK neurons contributes to tactile dysfunction and cognitive function.”

The results of this recent study could soon inspire other researchers to probe the link between tactile sensation and impaired mental functions in AD. If validated in future studies, they could eventually inform the development of alternative approaches to predict the progression of AD or even slow down the cognitive decline linked to the disease.

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