New Brain-Mapping Technique Pinpoints Cell Types Linked to Alzheimer's Progression

Researchers from The University of Texas at Arlington and the University of California–San Francisco have employed a novel brain-mapping technique to pinpoint memory-related brain cells that are susceptible to protein accumulation, a significant contributor to the onset of Alzheimer’s disease, an irreversible and progressive neurological disorder that gradually impairs memory and cognitive abilities.

In Texas, nearly half a million individuals are affected by Alzheimer’s disease, a type of dementia that incurs approximately $24 billion in caregiver expenses for the state, as reported by the Texas Department of State Health Services. Texas ranks fourth in the nation for the number of Alzheimer’s cases and second in deaths related to the disease.

To investigate why certain brain regions are more severely impacted by Alzheimer's disease, the researchers concentrated on tau, a protein that builds up in brain cells and interferes with normal functioning.

Utilizing the MISS (Matrix Inversion and Subset Selection) mapping technique, which analyzed around 1.3 million cells, the research team generated comprehensive maps of various cell types in mice's brains.

They compared these maps to regions where tau accumulates to determine which cell types are most affected. Their results are published in the journal Nature Communications Biology.

Using mathematical and computational models, we found that certain cells in the hippocampus, a brain area important for memory and navigation, are more vulnerable to tau buildup. These glutamatergic neurons showed a strong connection with tau deposits, meaning they are more likely to be affected. In contrast, brain cells in the cortex, the part of the brain that controls movement, sensory information, emotions, and reasoning were less likely to be affected by tau.”

  Pedro Maia, Study Author and Assistant Professor, Mathematics, University of Texas at Arlington

Interestingly, the researchers also found that oligodendrocytes, which are brain cells that assist in insulating nerve fibers, were less impacted by tau. This indicates that these cells may play a protective role against tau accumulation in the brain.

The study further revealed that the distribution of various cell types in the brain might be a better predictor of tau accumulation than genetic factors alone. This suggests that the presence of specific cell types in different brain regions could be more critical than Alzheimer ’s-related genes in determining susceptibility to tau.

Overall, this study helps us understand why certain brain regions are more affected by tau buildup leading to Alzheimer's disease. By identifying the cell types and gene functions involved, our study showcases how theoretical and computational models can provide new insights into the progression of Alzheimer’s disease. This is another piece of valuable data that will help us specifically target the vulnerable cells and genes associated with tau buildup, potentially slowing or preventing Alzheimer's disease progression in the future.”

Pedro Maia, Study Author and Assistant Professor, Mathematics, University of Texas at Arlington