Researchers from DZNE, Ludwig-Maximilians-Universität München, and Technical University of Munich have found that the enzyme “gamma-secretase” – implicated in Alzheimer’s disease and cancer – selects its reaction partners according to a complex scheme of molecular features.

It’s been recognized for some time that Alzheimer’s disease affects brain regions differently and that tau — a protein known to misbehave — plays an important role in the disease. Brain areas like the entorhinal cortex and hippocampus succumb early to tau tangles, while other areas, like the primary sensory cortices, remain resilient to the disease. In the quest to better understand this selective vulnerability (SV) or resilience (SR) to Alzheimer’s disease, researchers have looked to gene association and transgenic studies to identify Alzheimer’s risk genes. But past research has not shown a clear link between the location of genetic risk factors and associated tau pathology. Now, a new study by UC San Francisco researchers has made a leap toward answering that question — by combining brain imaging, genetics, and advanced mathematical modeling into a powerful new lens. The study, published July 9 in Brain, shows multiple distinct pathways by which risk genes confer vulnerability or resilience in Alzheimer’s disease.

Based on the analysis of the genotypes of 500 volunteers, the research project aims to develop a panel of prognostic biomarkers and differentiate Alzheimer’s disease from other types of dementia using blood tests.

UCLA Health researchers have identified four distinct pathways that lead to Alzheimer's disease by analyzing electronic health records, offering new insights into how the condition develops over time rather than from isolated risk factors.