The relationship between CSF biomarkers and cerebral metabolism in early-onset Alzheimer's disease

PurposeOne can reasonably suppose that cerebrospinal spinal fluid (CSF) biomarkers can identify distinct subgroups of Alzheimer's disease (AD) patients. In order to better understand differences in CSF biomarker patterns, we used FDG PET to assess cerebral metabolism in CSF-based subgroups of AD patients.MethodsEighty-five patients fulfilling the criteria for probable early-onset AD (EOAD) underwent lumbar puncture, brain F-18-FDG PET and MRI. A cluster analysis was performed, with the CSF biomarkers for AD as variables. Vertex-wise, partial-volume-corrected metabolic maps were computed for the patients and compared between the clusters of patients. Linear correlations between each CSF biomarker and the metabolic maps were assessed.ResultsThree clusters emerged. The A42 cluster contained 32 patients with low levels of A42, while tau and p-tau remained within the normal range. The A42+tau cluster contained 41 patients with low levels of A42 and high levels of tau and p-tau. Lastly, the tau cluster contained 12 patients with very high levels of tau and p-tau and low-normal levels of A42. There were no inter-cluster differences in age, sex ratio, educational level, APOE genotype, disease duration or disease severity. The A42+tau and tau clusters displayed more marked frontal hypometabolism than the A42 cluster did, and frontal metabolism was significantly negatively correlated with the CSF tau level. The A42 and A42+tau clusters displayed more marked hypometabolism in the left occipitotemporal region than the tau cluster did, and metabolism in this region was significantly and positively correlated with the CSF A42 level.ConclusionThe CSF biomarkers can be used to identify metabolically distinct subgroups of patients with EOAD. Future research should seek to establish whether these biochemical differences have clinical consequences.