Biomarkers

Background: Corticobasal syndrome (CBS) is a progressive neurodegenerative syndrome that can result from several underlying neuropathologies, including Alzheimer's disease (AD). Little is known about the utility of blood plasma measures to predict PET biomarker confirmed AD in CBS.

Method: Eighteen CBS patients (8 PET Aβ+; 10 PET Aβ-) and 8 cognitively unimpaired Aβ- individuals (CU) were recruited by the Neurodegenerative Research group from the Department of Neurology, Mayo Clinic, Rochester, MN, underwent Aβ (Pittsburgh Compound-B) and tau (¹⁸F-flortaucipir) PET and provided a blood sample. Blood plasma analysis was performed to assess p-tau 181, total tau, Aβ 42/40, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) using the Quanterix Simoa platform. Plasma concentrations were compared between Aβ-, and Aβ+ CBS and controls using Kruskal-Wallis corrected for multiple comparisons using Dunn's test, with effect size measured with area under the receiver operating characteristic curve (AUROC) analysis. Spearman correlations were calculated to assess relationships between plasma concentrations and Aβ and tau PET uptake.

Result: The CBS Aβ+ group showed reduced Aβ42/40 ratio, with elevated p-tau 181, GFAP and NfL plasma concentrations compared to CU, while the CBS Aβ- group only showed elevated NfL concentration compared to CU (Figure 1). Both p-tau 181 (AUROC=0.95) and GFAP (AUROC=0.91) plasma concentrations were able to differentiate CBS Aβ- from CBS Aβ+. Plasma p-tau 181 and GFAP concentrations showed a positive correlation to both Aβ and tau PET uptake, and the Aβ42/40 ratio showed a negative correlation to Aβ PET uptake (Figure 2). No correlations were observed between NfL and Aβ and tau PET.

Conclusion: This study supports the use of plasma p-tau 181 and GFAP to detect AD in CBS, while NfL shows potential as a nonspecific disease biomarker of CBS regardless of underlying pathology. Plasma concentrations of these biomarkers may potentially be incorporated into clinical trials targeting CBS patients with underlying AD pathology.