Summary: Women are at higher risk for Alzheimer’s disease and tend to experience faster progression, a finding linked to greater and more rapid brain-wide spread of the tau protein.
Source: Vanderbilt University Medical Center
Overview: The abnormal buildup of proteins in the brain is a hallmark of Alzheimer’s disease, but how these proteins spread across brain networks may help explain why the disease affects women more frequently and progresses more quickly in them than in men.
Researchers at the Center for Cognitive Medicine (CCI) at Vanderbilt University Medical Center examined differences in the behavior of tau, a protein closely associated with cognitive decline, and found that the pattern and pace of tau’s spread through the brain differ between sexes. Their analysis shows that women exhibit larger, brain-wide accumulations of tau that are linked to an accelerated spread across brain regions compared with men.
The team presented these findings at the Alzheimer’s Association International Conference, held July 14–18 in Los Angeles.
Evidence from recent studies supports the idea that tau propagates through brain tissue in a manner similar to an infectious process: it moves from neuron to neuron, converts otherwise healthy proteins into abnormal tangles, and ultimately contributes to neuron loss. To investigate how tau moves through the living brain, the Vanderbilt researchers used positron emission tomography (PET) data from cognitively normal adults and people with mild cognitive impairment enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
Using graph theory and network modeling, the researchers reconstructed in vivo maps of tau spread. These mathematical networks reveal how tau appears to travel between connected brain regions over time, offering insight into pathways of disease propagation that static measures of protein burden alone cannot provide.
“It’s like piecing together what happened after the fact,” said Sepi Shokouhi, Ph.D., assistant professor of Psychiatry and Behavioral Sciences and lead investigator. “Even if you did not observe the spread directly, the network analysis can indicate where tau likely entered the system and which regions it reached next.”
“The graph analysis does something similar to show how tau spreads from one region to another.”
The network models revealed notable sex differences in tau architecture. Women’s tau networks showed a larger number of bridging regions—nodes that connect distinct communities of brain regions—than men’s networks. These bridges may provide routes that allow tau to move more readily between otherwise separate brain systems, increasing both the speed and extent of accumulation. That pattern offers a plausible mechanism for the higher prevalence and faster clinical progression of Alzheimer’s disease observed in women.
If further research confirms that tau spreads more rapidly across women’s brains, the findings could have important implications for prevention and treatment. A sex-specific approach might include earlier therapeutic interventions, tailored lifestyle recommendations, and cognitive strategies designed to delay or mitigate the effects of tau accumulation. The authors emphasize that additional studies are needed to validate these network-based models and to determine how best to translate them into clinical practice.
“Understanding how biological differences shape memory and cognition is essential,” said Shokouhi. “Sex-specific patterns in brain pathology, anatomy, and function may map onto distinct cognitive outcomes. Recognizing those differences can help explain why neurodegenerative disorders are more common or progress differently in men and women, and guide the development of more effective, individualized treatments.”
Funding: This research was supported by National Institutes of Health (NIH) grants R00 EB009106, K24 MH110598 and R01 AG047992.
Source:
Vanderbilt University Medical Center
Media Contacts:
Craig Boerner – Vanderbilt University Medical Center
Image Source:
The image is in the public domain.
Original Research: The findings were presented at the Alzheimer’s Association International Conference, 2019, in Los Angeles, California.