Relationships between biomarkers in aging and dementia

Abstract

Background: PET imaging using [¹⁸F]fluorodeoxyglucose (FDG) and [¹¹C]Pittsburgh compound B (PIB) have been proposed as biomarkers of Alzheimer disease (AD), as have CSF measures of the 42 amino acid β-amyloid protein (Aβ_1-42) and total and phosphorylated tau (t-tau and p-tau). Relationships between biomarkers and with disease severity are incompletely understood. Methods: Ten subjects with AD, 11 control subjects, and 34 subjects with mild cognitive impairment from the Alzheimer’s Disease Neuroimaging Initiative underwent clinical evaluation; CSF measurement of Aβ_1-42, t-tau, and p-tau; and PIB-PET and FDG-PET scanning. Data were analyzed using continuous regression and dichotomous outcomes with subjects classified as “positive” or “negative” for AD based on cutoffs established in patients with AD and controls from other cohorts. Results: Dichotomous categorization showed substantial agreement between PIB-PET and CSF Aβ_1-42 measures (91% agreement, κ = 0.74), modest agreement between PIB-PET and p-tau (76% agreement, κ = 0.50), and minimal agreement for other comparisons (κ 1-42. Regression models adjusted for diagnosis showed that PIB-PET was significantly correlated with Aβ_1-42, t-tau, and p-tau_181p, whereas FDG-PET was correlated only with Aβ_1-42. Conclusions: PET and CSF biomarkers of Aβ agree with one another but are not related to cognitive impairment. [¹⁸F]fluorodeoxyglucose-PET is modestly related to other biomarkers but is better related to cognition. Different biomarkers for Alzheimer disease provide different information from one another that is likely to be complementary.