Decreased CSF levels of L-carnitine in non-apolipoprotein E4 carriers at early stages of Alzheimer ́s disease

Running title: CSF L-carnitine levels along AD progression. ABSTRACT Increasing evidences suggest that Alzheimer´s disease (AD) is a heterogeneous disorder that includes several subtypes with different aetiology and progression. Cerebrospinal fluid (CSF) is being used to find new biomarkers reflecting the complexity of the disease´s pathological pathways. We used CSF and clinical data from patients to investigate the status of asymmetric dimethyl–L-arginine, creatine, suberylglycine and L-carnitine along AD progression. These molecules play important roles on mitochondrial function and dysfunctions in mitochondrial metabolism are involved in AD pathology. We found that non-apolipoprotein E4 carriers show lower levels of L-carnitine in CSF early in AD. L-carnitine levels correlate with Aβ 42 levels and MMSE score, but do not add specificity or sensitivity to the classical AD CSF biomarkers, Aβ 42 , phospho-Tau and total-Tau. Our results suggest apoE genotype-depending differences in L-carnitine synthesis or metabolism along AD, and insinuate that L-carnitine treatments would be more beneficial for AD patients not carrying the apoE4 isoform.