Head-to-head comparison of plasma p-tau181, p-tau231 and glial fibrillary acidic protein in clinically unimpaired elderly with three levels of APOE4-related risk for Alzheimer's disease

• Published in: Neurobiology of disease Vol. 183; p. 106175
• Main Authors: Snellman, Anniina, Ekblad, Laura L., Ashton, Nicholas J., Karikari, Thomas K., Lantero-Rodriguez, Juan, Pietilä, Elina, Koivumäki, Mikko, Helin, Semi, Karrasch, Mira, Zetterberg, Henrik, Blennow, Kaj, Rinne, Juha O.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2023; Elsevier
• Subjects: Aged; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer's disease; Amyloid beta-Peptides; APOE; Apolipoprotein E; Apolipoprotein E3; Apolipoprotein E4 - genetics; beta-amyloid; Biomarker; Biomarkers; Blood biomarkers; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - genetics; GFAP; Glial Fibrillary Acidic Protein; Humans; Neurosciences; Neurovetenskaper; P-tau181; P-tau231; Preclinical; tau Proteins; Biomarker; AD; CNS; P-tau181; Simoa; p-tau; GFAP; Blood biomarkers; P-tau231; beta-amyloid; APCC; Aβ; VOI; Apolipoprotein E; MMSE; CSF; SUVR; Preclinical; APOE; Alzheimer's disease; PET
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2023.106175

Plasma phosphorylated tau (p-tau) and glial fibrillary acidic protein (GFAP) both reflect early changes in Alzheimer's disease (AD) pathology. Here, we compared the biomarker levels and their association with regional β-amyloid (Aβ) pathology and cognitive performance head-to-head in clinically unimpaired elderly (n = 88) at three levels of APOE4-related genetic risk for sporadic AD (APOE4/4 n = 19, APOE3/4 n = 32 or non-carriers n = 37). Concentrations of plasma p-tau181, p-tau231 and GFAP were measured using Single molecule array (Simoa), regional Aβ deposition with 11C-PiB positron emission tomography (PET), and cognitive performance with a preclinical composite. Significant differences in plasma p-tau181 and p-tau231, but not plasma GFAP concentrations were present between the APOE4 gene doses, explained solely by brain Aβ load. All plasma biomarkers correlated positively with Aβ PET in the total study population. This correlation was driven by APOE3/3 carriers for plasma p-tau markers and APOE4/4 carriers for plasma GFAP. Voxel-wise associations with amyloid-PET revealed different spatial patterns for plasma p-tau markers and plasma GFAP. Only higher plasma GFAP correlated with lower cognitive scores. Our observations suggest that plasma p-tau and plasma GFAP are both early AD markers reflecting different Aβ-related processes. •Plasma p-tau181 and p-tau231 levels increase already in healthy APOE4 carriers.•Plasma p-tau markers and GFAP all associate with brain beta-amyloid load.•Only plasma GFAP associated with cross-sectional cognitive performance.•Plasma p-tau markers and plasma GFAP seem to reflect different Aβ related processes.