Is imaging of tau the preferable marker of cognitive impairment in AD? DEBATE

Department of Psychiatry, University of Geneva School of Medicine, 2, ch Petit Bel-Air, 1225 Geneva, Switzerland Early clinic-pathological studies demonstrated that the two cardinal lesions associated with Alzheimer disease (AD), neurofibrillary tangles (NFT) and amyloid deposits, have a differential impact on cognition both at early and late stages of the neurodegenerative process. In contrast to ß-amyloid (Aß) deposition that occurs diffusely in the human brain over 60 years of age, NFT formation follows hierarchical schemes of regional and cellular vulnerability affecting first the entorhinal cortex and parahippocampal formation before moving in adjacent neocortical association areas. Long before the emergence of novel imaging techniques, it was clear that Aß deposits correlate very weekly with cognition and downstream neurodegenerative biomarkers. In contrast, NFT and associated synaptic loss is strictly related to the loss of cognitive functions not only at late but also at early stages of AD. The last decade was characterized by the exponential increase of knowledge in the field of AD predictive biomarkers and, most importantly, characterization of tracers for ß-amyloid (Aß). It is now widely acknowledged that amyloid deposits in positron emission tomography (PET) with Pittsburg compound B (PiB; a marker of Aß fibrillar deposits) precede dementia by 5-10 years, and PiB burden inversely correlates with concentration of Aβ42 in the cerebro-spinal fluid. However, increased PiB burden was reported in nearly 20% to 30% of controls in the general population pointing to the fact that Aß deposition is not sufficient to cause cognitive decline in AD. Moreover, the rate of Aß accumulation is not related to neurodegeneration