Summary: Researchers have identified memory-related brain cells that are extremely vulnerable to the accumulation of TAU protein, a key factor in Alzheimer’s disease. Miss brain mapping technology was used to profile 1.3 million cells in mice to determine which cell types are most affected.
Their findings indicate that glutamatergic neurons in the hippocampus are particularly susceptible, whereas cortical neurons and oligodendrocytes appear to be more resistant. Surprisingly, the distribution of brain cell types better predicted tau accumulation than genetic risk factors.
This suggests that not only genetics but cellular composition plays an important role in the progression of Alzheimer’s disease. This study provides valuable insights that may guide future efforts to delay or prevent disease.
Important Facts:
Cell type vulnerability: Glutamatechergic neurons in the hippocampus are prone to tau accumulation. Protective Brain Cells: Oligodendrocytes appear unaffected and play a potentially protective role.
Source: UT Arlington
Researchers at the University of Texas at Arlington and University of California San Francisco have used new brain mapping techniques to identify memory-related brain cells that are vulnerable to protein accumulation, a key factor in the development of memory impairment.
Nearly half a million people live with Alzheimer’s disease in Texas, according to the Texas Department of Health.
Texas ranks fourth in the nation for Alzheimer’s disease and second in Alzheimer’s disease-related deaths.
To understand why certain parts of the brain are more affected by Alzheimer’s disease, researchers focused on tau, a protein that accumulates in brain cells and destroys normal activity.
Using MISS (Matrix Inversion and Subset Selection) mapping technology, which introduced approximately 1.3 million cells, the researchers created a detailed map of different cell types in the mouse brain. They compared these maps to areas where Tau constructs to identify which cell types are most affected.
Their findings are published in the peer-reviewed journal Nature Communications Biology.
“Using mathematical and computational models, we found that certain cells in the hippocampus, a brain region important for memory and navigation, are more vulnerable to tau accumulation,” says Pedro Maia, assistant professor of mathematics at UTA.
“These glutamatergic neurons showed strong connections to tau deposits, meaning they are more likely to be affected. In contrast, cortical brain cells (part of the brain that controls movement, sensory information, emotions, and inference) were less likely to be affected by tau.”
Interestingly, the researchers also found that oligodendrocytes, brain cells that help sequester nerve fibers, are less susceptible to tau. This suggests that these cells may help protect the brain from tau accumulation.
The study also found that the distribution of different cell types in the brain could better predict where tau accumulation occurs than genetic factors alone. This means that the types of cells present in different brain regions may be more important than Alzheimer’s disease-related genes in determining vulnerability to tau.
“Overall, this study will help us understand why certain brain regions are more affected by the accumulation of tau, which leads to Alzheimer’s,” Dr. Maia said.
“By identifying relevant cell types and gene functions, our study demonstrates how theoretical and computational models can provide new insights into the progression of Alzheimer’s disease.
“This is another part of valuable data that will help specifically target vulnerable cells and genes associated with TAU accumulation, and could potentially slow or prevent future progression of Alzheimer’s disease.”
For more information about MAIA’s work, check out the NSF RTG training at the Mathematics for Human Health Program. He is a co-leading leader in computational neurology.
Funding: This work was supported by the following NIH grants: R01NS092802, RF1AG062196 and R01AG072753.
This brain mapping and research news on Alzhimer’s disease
Author: Katherine Bennett
Source: UT Arlington
Contact: Catherine Bennett – UT Arlington
Image: Image credited to Neuroscience News
Original research: Open access.
“Searching the cellular basis for selective vulnerability to taopathic insults in Alzheimer’s disease,” Pedro Maia et al. Communication biology
Abstract
Searching for the cellular basis for selective vulnerability to taopathic insults in Alzheimer’s disease
Neurodegenerative diseases such as Alzheimer’s disease show pathological changes in the brain that progress in stereotypical and regionally specific ways. However, the cell foundation of regional vulnerability is poorly understood as the whole brain map of a comprehensive collection of cell types is inaccessible.
Here, we unfolded a recent cell type mapping pipeline, matrix inversion, and subset selection (MISS) to determine the brain-wide distribution of mouse pan-hepocampal and neocortical cells, and used these maps to identify the general principles of cell type-based selective vulnerability in the PS19 mouse model.
We found that cortical glutamatergic and GABAergic neurons are significantly positively associated with local tau deposition, suggesting fragility, while cortical glutamatergic and GABAergic neurons are negatively associated.
We also identified oligodendrocytes as one of the most strongly associated cell types. Furthermore, cell type distribution predicted end-time Tau pathology rather than adrisk gene expression.
Using gene ontology analysis, we found that genes directly correlated with tau pathology functionally differ from genes that constitutively and specifically embody vulnerable cells.
In short, we are elucidating cell type correlations of tau deposition across mouse models of taupathy and promoting an understanding of selective cell vulnerability at the whole brain level.
