Advanced imaging of tau pathology in Alzheimer Disease: New perspectives from super resolution microscopy and label-free nanoscopy.
Alzheimer's disease (AD) is the main cause of dementia in the elderly population. Over 30 million people worldwide are living with dementia and AD prevalence is projected to increase dramatically in the next two decades. In terms of neuropathology, AD is characterized by two major cerebral hallmarks: extracellular β-amyloid (Aβ) plaques and intracellular Tau inclusions, which start accumulating in the brain 15-20 years before the onset of symptoms. Within this context, the scientific community worldwide is undertaking a wide research effort to detect AD pathology at its earliest, before symptoms appear. Neuroimaging of Aβ by positron emission tomography (PET) is clinically available and is a promising modality for early detection of Aβ pathology and AD diagnosis. Substantive efforts are ongoing to develop advanced imaging techniques for early detection of Tau pathology. Here, we will briefly describe the key features of Tau pathology and its heterogeneity across various neurodegenerative diseases bearing cerebral Tau inclusions (i.e., tauopathies). We will outline the current status of research on Tau-specific PET tracers and their clinical development. Finally, we will discuss the potential application of novel super-resolution and label-free techniques for investigating Tau pathology at the experimental level and their potential application for AD diagnosis. Microsc. Res. Tech. 79:677-683, 2016. © 2016 Wiley Periodicals, Inc.
Department of Chemical Engineering and Biotechnology, Pembroke Street, University of Cambridge, Cambridge, CB2 3RA, United Kingdom.
Gabriele S Kaminski
GS
Schierle
Department of Chemical Engineering and Biotechnology, Pembroke Street, University of Cambridge, Cambridge, CB2 3RA, United Kingdom.
Claire H
CH
Michel
Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Via Morego 30, Genova, Italy.
Laura
L
Gasparini
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008853:Microscopy; D057054:Molecular Imaging; D036103:Nanotechnology; D016875:tau Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism
D000682:Amyloid; D016875:tau Proteins
Alzheimer; label-free imaging; nanoscopy; tauopathy