Symptomatic and preclinical Alzheimer’s disease: Neuropathology and imaging

The current gold standard for the diagnosis of Alzheimer’s disease (AD) is the pathological examination at autopsy. Clinical diagnostic procedures are quite well developed for symptomatic AD and permit a reliable and valid identification of AD patients. Today, there is strong interest to diagnose AD already in a preclinical stage to include protective treatment strategies into the treatment regimes for AD. This is important because current therapies for AD mainly focus on symptomatic improvement rather than on delaying disease progression. The current diagnostic criteria for preclinical AD (preAD) rely on biomarker profiles indicative for AD in non-demented individuals. At autopsy, pathological lesions considered to represent AD pathology permit the classification of non-demented cases exhibiting AD pathology as pathologically-defined preAD (p-preAD) cases. Recent studies investigating amyloid imaging as a biomarker and comparing it with the post-mortem findings on AD pathology revealed that preAD cases identified clinically by amyloid imaging already exhibited advanced stages of AD pathology whereas p-preAD cases with initial AD lesions failed clinical detection. In this article I will discuss these findings and its potential impact on clinical studies aimed at stopping or delaying the progression from preAD to symptomatic AD as well as on the interpretation of imaging or biomarker data in relation to the underlying disease progress with a focus on propagation and maturation of Aβ and τ pathology in-p-preAD.