Although its main biological function is still unknown, the prion protein is involved in normal synaptic function.1Interestingly, the presence of a valine (V), replacing a methionine (M) at codon 129 of the prion protein gene (PRNP), has been associated with poor performance in cognitive tests in a large cohort of aged, non-demented, French people.2 Accordingly, this polymorphic gene represents a suitable candidate for an association with Alzheimer's disease, a dementing disorder characterised by neuronal degeneration and synaptic loss. To assess whether the PRNP V/M codon129 polymorphism—alone or in combination with polymorphisms in the apolipoprotein (APO)E3 and interleukin (IL)-1α4 genes, already shown to be associated with Alzheimer's disease—affects the occurrence or clinical features of the disease, we performed a case-control study in a cohort of Italian patients with sporadic Alzheimer's disease and age matched healthy controls.

Venous blood was collected from 212 Italian patients (130 women, 82 men; mean (SD) age at disease onset 68.3 (8.0) years) affected by clinically probable Alzheimer's disease, according to McKhann's criteria. Patients were also divided into those with early disease onset (⩽65 years; 72 patients; mean (SD) age at disease onset 57.0 (7.5) years), and those with a late onset (>65 years; 140 patients; mean (SD) age …