In cognitively unimpaired older adults aged 65–85, depressive symptoms are associated with higher amygdalar tau burden among individuals who are amyloid-positive, but not among those who are amyloid-negative.

When amyloid plaques are present in the brain, they trigger chronic inflammation and weaken the brain's ability to clear toxic proteins. This creates a vulnerable environment where stress from depression or poor sleep activates the stress hormone system, which increases the production and sticking together of tau protein in the amygdala. At the same time, the brain's cleanup system slows down during poor sleep, letting tau build up even more. People with a specific gene variant called APOE ε4 have even weaker cleanup and stronger inflammation, making this process worse. The amygdala, which handles emotions, becomes a hotspot for tau buildup only when all these conditions are present together.