In humans, KL-VS heterozygosity has been associated with a reduced burden of amyloid and tau pathology in Alzheimer’s disease (AD) (Erickson et al., 2019; Belloy et al., 2020, 2021; Neitzel et al., 2021; Ali et al., 2022; Driscoll et al., 2022; Grøntvedt et al., 2022), potentially offsetting the negative effect of apolipoprotein E (APOE)-ε4 carrier status (Erickson et al., 2019; Belloy et al., 2020, 2021; Tank et al., 2021; Chen et al., 2023), one of the most well-established genetic risk factors for AD. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.