Synapse loss and synaptic dysfunction in Alzheimer’s disease (AD) are linked to membrane loss and altered membrane composition. Neurons require specific nutrients for the formation and maintenance of synaptic membranes. These nutrients fuel the metabolic pathways that synthesize new phospholipids, the main constituents of membranes. While AD patients may benefit from higher availability of the phospholipid-synthesizing nutrients that can support synapse formation and function, many patients have lower plasma levels of these nutrients. Such compromised nutritional status may progress during the course of the disease and may already be evident in earlier stages of AD. We aimed to investigate the role of these potential biomarkers in the pre-dementia stages of AD as well as in AD.
We currently investigate whether blood and cerebrospinal fluid (CSF) levels of phospholipid-synthesizing nutrients differentiate between subjects with subjective memory complaints (n=150), mild cognitive impairment (n=150), or AD (n=150) in a retrospective cohort study. Subjects were selected from the memory clinic based Amsterdam Dementia Cohort of the VUmc Alzheimer Center.
Analyses of paired CSF, serum, and plasma samples of the Amsterdam Dementia Cohort are ongoing. Among others, levels of the following nutrients are being measured: plasma and CSF choline, folic acid, uridine, and homocysteine and plasma polar lipid profile.
The current study may further elucidate the role of these nutrients in AD pathology by identifying their levels in plasma and CSF at different stages of the disease. In addition, these nutrients may have potential to serve as (modifiable) biomarkers for AD.