In addition, mutations in the presenilin (PS) gene (e.g., PS1-M146L, PS1-L166P, PS1-I213T, PS2-N141I, and etc.)increasing Aβ42/Aβ40 ratios have been identified as causative factors of the AD plaques leading to the aggressive forms of AD. The gene discussed is PRB2; the disease is Alzheimer disease.