BACKGROUND: PET imaging of the translocator protein (TSPO) is used to assess in vivo brain inflammation. One of the main methodological issues with this method is the allelic dependence of the radiotracer affinity. In Alzheimer's disease (AD), previous studies have shown similar clinical and patho-biological profiles between TSPO genetic subgroups. However, there is no evidence regarding the effect of the TSPO genotype on cerebrospinal-fluid biomarkers of glial activation, and synaptic and axonal damage. METHOD: We performed a trans-sectional study in early AD to compare cerebrospinal-fluid levels of GFAP, YKL-40, sTREM2, IL-6, IL-10, NfL and neurogranin between TSPO genetic subgroups. RESULTS: We recruited 33 patients with early AD including 16 (48%) high affinity binders, 13 (39%) mixed affinity binders, and 4/33 (12%) low affinity binders. No difference was observed in terms of demographics, and cerebrospinal fluid levels of each biomarker for the different subgroups. CONCLUSION: TSPO genotype is not associated with a change in glial activation, synaptic and axonal damage in early AD. Further studies with larger numbers of participants will be needed to confirm that the inclusion of specific TSPO genetic subgroups does not introduce selection bias in studies and trials of AD that combine TSPO imaging with cerebrospinal fluid biomarkers.
The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer's disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression.
