How golden is the gold standard of neuropathology in dementia?

Abstract

Current Alzheimer's disease (AD) criteria state that a definite diagnosis can only be made by postmortem examination. The neuropathological confirmation is often referred to as the "gold standard." In this article, we review what constitutes a gold standard and how the neuropathological examination of AD lives up to that standard. We conclude that there is no evidence for this notion because results between different laboratories differ to an important extent, especially when the clinical picture is in doubt, for example, when the dementia is mild. As an alternative, we propose to abandon thinking in standards and value neuropathology as any other biomarker, and to strive to use and integrate multiple sources of information to make the diagnosis of AD in all its complexity.