FIGURE 2: Major effects of Aβ aggregates on mitochondrial Ca²⁺ homeostasis in neurons. In physiological conditions, mitochondria take up Ca²⁺ from the cytosol via the MCU to produce ATP among other functions. In AD, Aβ aggregates (particularly soluble Aβ) increase mitochondrial Ca²⁺ via the MCU in vivo. This leads to mitochondrial Ca²⁺ overload and activates mPTP and caspases, which can trigger neuronal cell death via apoptosis. Blocking the MCU with Ru360 inhibits mitochondrial Ca²⁺ uptake, pointing to the MCU as a potential target for therapeutics aimed at preventing or reversing the progression of AD.