Translocator protein (TSPO) genotype does not change cerebrospinal fluid levels of glial activation, axonal and synaptic damage markers in early Alzheimer’s disease

• Published in: NeuroImage clinical Vol. 43; p. 103626
• Main Authors: Gouilly, Dominique, Vrillon, Agathe, Bertrand, Elsa, Goubeaud, Marie, Catala, Hélène, Germain, Johanne, Ainaoui, Nadéra, Rafiq, Marie, Nogueira, Leonor, Mouton-Liger, François, Planton, Mélanie, Salabert, Anne-Sophie, Hitzel, Anne, Méligne, Déborah, Jasse, Laurence, Sarton, Benjamine, Silva, Stein, Lemesle, Béatrice, Péran, Patrice, Payoux, Pierre, Thalamas, Claire, Paquet, Claire, Pariente, Jérémie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2024; Elsevier
• Subjects: Alzheimer’s disease; Cerebrospinal fluid; Neuro-inflammation; Regular; Rs6971; TSPO; Neuro-inflammation; AD; Alzheimer’s disease; Rs6971; HAB; Cerebrospinal fluid; LAB; YKL-40; IL-6; IL-10; GFAP; MAB; NfL; CSF; TSPO; sTREM2; PET
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2024.103626

•Glial activation, synaptic and axonal damage are not affected by TSPO genotype in AD.•Studies can combine TSPO PET and CSF biomarkers for a selected TSPO phenotype in AD.•Results from one TSPO phenotype might be generalizable to an entire AD population. 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. 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. 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. 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.