Association of PET-based stages of amyloid deposition with neuropathological markers of Aβ pathology

Abstract

Objective: To determine if PET-based stages of regional amyloid deposition are associated with neuropathological phases of Aβ pathology.

Methods: We applied data-driven regional frequency-based and a-priori striatum-based PET staging approaches to ante-mortem 18F-Florbetapir-PET scans of 30 cases from the Alzheimer's Disease Neuroimaging Initiative autopsy cohort, and used Bayesian regression analysis to study the associations of these in vivo amyloid stages with neuropathological Thal phases of regional Aβ plaque distribution and with semi-quantitative ratings of neocortical and striatal plaque densities.

Results: Bayesian regression revealed extreme evidence for an association of both PET-based staging approaches with Thal phases, and these associations were about 44 times more likely for frequency-based stages and 89 times more likely for striatum-based stages than for global cortical 18F-Florbetapir-PET signal. Early (i.e., neocortical-only) PET-based amyloid stages also predicted the absence of striatal/diencephalic cored plaques. Receiver operating characteristics curves revealed highly accurate discrimination between low/high Thal phases and the presence/absence of regional plaques. The median areas under the curve were 0.99 for frequency-based staging (95% credibility interval 0.97-1.00), 0.93 for striatum-based staging (0.83-1.00), and 0.87 for global 18F-Florbetapir-PET signal (0.72-0.98).

Interpretation: Our data indicate that both regional frequency- and striatum-based amyloid-PET staging approaches were superior to standard global amyloid-PET signal for differentiating between low and high degrees of regional amyloid pathology spread. Despite this, we found no evidence for the ability of either staging scheme to differentiate between low and moderate degrees of amyloid pathology which may be particularly relevant for early, preclinical stages of Alzheimer's disease.