ACAA1 and early-onset autosomal dominant Alzheimer disease: In order to investigate which variant might be associated with EOFAD, we screened for these 58 potentially damaging variants in the whole-exome sequencing data of 169 patients with EOFAD that were reported in our previous studies.21,30 The ACAA1 variant (GenBank: NM_001130410.1: c.896T>C, rs117916664, p.N299S; PHRED-scaled Combined Annotation-Dependent Depletion (CADD) score31 19.72), which was homozygous in the AD proband (Fig. 1a), was significantly enriched in EOFAD patients (MAF = 0.0525) compared to controls (MAF = 0.0204) (OR = 2.662, P value = 9.85 × 10−3).