Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder, but still without known disease mechanism, proper treatment and efficient diagnostic tools for an early stage diagnosis. There is increasing evidence that lipids, especially cholesterol and sphingolipids, may play a role in pathological processes that occur in the AD brain even in very early stages of the disease. However, lipid changes in cerebrospinal fluid (CSF) of individuals with AD have not been well studied. In previous work, we developed a reproducible and sensitive nano-HPLC-MS method for CSF phospholipids screening and conducted a pilot study to find potential phospholipid changes in CSF from individuals with AD dementia. We observed a slight increase (24%) of sphingomyelin (SM) in CSF samples from patients with probable AD compared to non-demented controls. The goal of this work was to validate our findings and to analyze how SM CSF levels change in different stages of AD from prodromal to mild and moderate AD. We found significantly increased SM levels (50.4±11.2%, p=0.003) in the CSF from individuals with prodromal AD compared to cognitively normal controls, but no change in CSF SM levels between mild and moderate AD groups and cognitively normal controls. These results suggest that alterations in the SM metabolism may contribute to early pathological processes leading to AD.