Tau imaging in preclinical Alzheimer’s disease

Abstract

Aggregated tau is a major neuropathological protein implicated in the pathophysiology of common neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease without (PD) and with later dementia (PDD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and corticobasal degeneration (CBD). Aggregated tau tangles, the result of hyperphosphorylation, is a pathological characteristic of a group of neurodegenerative conditions known as the tauopathies. In AD, it has been shown that the density of tau tangles closely correlates with neuronal dysfunction and cell death, which is not the case for β-amyloid. Until now, diagnostic and pathological demonstration of tau deposition has only been possible by invasive techniques such as brain biopsy or postmortem examination. The recent advances in the development of selective tau positron emission tomography (PET) tracers have allowed in vivo investigation of the presence and extent of tau pathology in patients suspected of having tauopathies and the role of tau in the early phases of neurodegenerative diseases. In this review, the role of aggregated tau will be discussed, as well as the challenges posed by, and the current status of, the development of selective tau tracers as biomarkers, and the new clinical information that has been uncovered, in addition to the opportunities for refining the diagnosis of tauopathies in the future.