In the brains of individuals with Alzheimer’s disease, we have used the following four independent methods to document low ATM function: reduction in ATM immunostaining intensity; nuclear translocation of HDAC4; elevation of trimethylation on lysine 27 of histone H3 (H3K27me3); and the appearance of cell cycle proteins, specifically cyclin A2. Here, CCNA2 is linked to early-onset autosomal dominant Alzheimer disease.