What about neurons?
Among the many diverse neuronal subtypes, we found those that regulate sleep and circadian rhythms were hit hardest in AD. Their cellular communication pathways showed major disruptions (e.g., ligand-receptor interactions).
What about neurons?
Among the many diverse neuronal subtypes, we found those that regulate sleep and circadian rhythms were hit hardest in AD. Their cellular communication pathways showed major disruptions (e.g., ligand-receptor interactions).
Zooming in on inflammation, we focused on microglia (the brain's immune cells).
We mapped their transition from a healthy state to a disease-associated state, finding they become progressively more inflammatory and stress-responsive along the AD trajectory.
Zooming in on inflammation, we focused on microglia (the brain's immune cells).
We mapped their transition from a healthy state to a disease-associated state, finding they become progressively more inflammatory and stress-responsive along the AD trajectory.
Our machine learning models, trained to distinguish AD from control cells, pointed to two key predictors of disease:
inflammation and disruptions in circadian rhythm regulators.
Our machine learning models, trained to distinguish AD from control cells, pointed to two key predictors of disease:
inflammation and disruptions in circadian rhythm regulators.
To see which cells were responsible, we performed single-nucleus RNA-seq on 614,403 nuclei from post-mortem hypothalamus from young, AD, and age-matched non-dementia controls.
To see which cells were responsible, we performed single-nucleus RNA-seq on 614,403 nuclei from post-mortem hypothalamus from young, AD, and age-matched non-dementia controls.
Brain imaging of 202 individuals revealed that different hypothalamic subregions change differently with age.
The most affected areas are linked to stress, energy, and circadian rhythms, and these changes were exacerbated in AD, showing the hypothalamus is not a single unit.
Brain imaging of 202 individuals revealed that different hypothalamic subregions change differently with age.
The most affected areas are linked to stress, energy, and circadian rhythms, and these changes were exacerbated in AD, showing the hypothalamus is not a single unit.