Family history is one of the biggest risk factors—behind advanced age—for developing late-onset Alzheimer disease (AD). This is especially true if the family history involves a first-degree relative, such as a parent, increasing AD risk by at least 2- to 4-fold.¹ Several questions arise. Do parents transmit AD risk? If so, who is to blame? Why does it matter?

A history of parents with AD increases risk in offspring for reasons that may be biological, sociocultural, or both. In late-onset AD, mounting studies support a preferential risk of developing AD with a maternal, but not paternal, history of the disease. Maternal transmission of AD may be rooted in biological origins (Figure) related to passing on the maternal X chromosome, mitochondria, and specific genomic imprinting (or silencing of genes) to offspring. More maternal history of AD in a family could also result from gender disparities and secular trends. For example, in studies to date, the generations of women with AD had less access to and systematically experienced less formal education compared with men, potentially decreasing brain reserve. Thus, it may seem justified, although not fair, to blame your mom for part of your AD risk.