C3 and Alzheimer disease: Elevated C3 levels in HAND and Aβ + brains are also consistent with studies showing that reactive astrocytes produce C3 (Liddelow et al., 2017; Nitkiewicz et al., 2017; Clarke et al., 2018; Vallee and Fields, 2022) and may contribute to metabolic deficiencies in neurons in HAND and AD (Jiang and Cadenas, 2014; Yin et al., 2016; Fields et al., 2019; Swinton et al., 2019).