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

One 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.

Eighty-five patients fulfilling the criteria for probable early-onset AD (EOAD) underwent lumbar puncture, brain ¹⁸F-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.

Three clusters emerged. The “Aβ42” cluster contained 32 patients with low levels of Aβ42, while tau and p-tau remained within the normal range. The “Aβ42 + tau” cluster contained 41 patients with low levels of Aβ42 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 Aβ42. There were no inter-cluster differences in age, sex ratio, educational level, APOE genotype, disease duration or disease severity. The “Aβ42 + tau” and “tau” clusters displayed more marked frontal hypometabolism than the “Aβ42” cluster did, and frontal metabolism was significantly negatively correlated with the CSF tau level. The “Aβ42” and “Aβ42 + 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 Aβ42 level.

The 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.