Neuropeptide Y (NPY) is a neurotransmitter expressed in the central nervous system and involved in learning and memory. The NPY L7P polymorphism has been associated with altered cholesterol levels in obese patients. Since altered cholesterol metabolism is also involved in Alzheimer's disease (AD), the effects of two NPY polymorphisms (L7P and IVS1-100 T/G) on CSF and plasma cholesterol and 24S-hydroxycholesterol were investigated in AD patients and non-demented controls. Furtheremore, the effect of both NPY polymorphisms on the risk of AD was studied.The NPY IVS1-100 T/G polymorphism influenced CSF levels of cholesterol, whereas CSF and plasma levels of 24S-hydroxycholesterol and plasma cholesterol were not altered by genotype. NPY L7P polymorphism did not influence CSF or plasma cholesterol or 24S-hydroxycholesterol. Both NPY polymorphisms did not influence the risk of AD. Our data support the observation, that NPY polymorphisms might influence cholesterol metabolism, but might not act as major risk factor in AD.