Familial Risk of Dementia Associated With a Biologic Subtype of Alzheimer's Disease

• Increased platelet membrane fluidity is a stable familial trait that identifies a prominent subgroup of patients with Alzheimer's disease. Patients in this subgroup have distinct clinical features, including an early age at symptomatic onset and a rapidly progressive course. The morbid risk of Alzheimer's-type dementia was studied in 421 first-degree relatives of 43 patients who met current consensus criteria for probable Alzheimer's disease and 47 healthy controls. Relatives of patients showed an approximate 50% (90- to 95-year) lifetime risk of dementia, regardless of the platelet membrane phenotype of the respective proband, which was over four times the control value. However, relatives of patients with increased platelet membrane fluidity who developed dementia exhibited symptoms significantly earlier than relatives of patients with normal platelet membrane fluidity. Alternative genetic models that describe the relationship of platelet membrane fluidity and Alzheimer's disease are discussed.