One of the durable puzzles in Alzheimer's research is that some people have the pathology and never lose their memory. Plaques and tangles show up in the postmortem tissue of people who were sharp into their hundreds.
A study released July 26 in Nature Medicine goes after that gap directly [1].
Researchers at the VIB-KU Leuven Center for Neuroscience, working with KU Leuven, the UK Dementia Research Institute and Muna Therapeutics, mapped six distinct tissue domains in postmortem brain tissue, each representing a stage of the disease's progression [1].
What they found sits at the point where amyloid-beta gives way to tau. Co-senior authors Bart De Strooper and Mark Fiers report that the response of microglia - the brain's own immune cells - at that inflection point tracks with whether a person develops dementia or stays cognitively resilient. Plaque and tangle burden alone does not [1].
The resilient group in the data includes cognitively healthy centenarians [1] - people whose brains carried the disease and whose minds did not.
This is a map, not a treatment, and the distance between the two is measured in years. What a map gives you is a place to aim: if the divergence happens at a specific moment in a specific cell type, that moment is a target.
