Neurodegeneration, the progressive loss of neurons, is a major process involved in dementia and agerelated cognitive impairment. It can be detected clinically using currently available biomarker tests. Suspected Non Alzheimer Pathology (SNAP) is a biomarker-based concept that encompasses a group of individuals with neurodegeneration, but no evidence of amyloid deposition (thereby distinguishing it from Alzheimer’s disease (AD)). These individuals may often have a clinical diagnosis of AD, but their clinical features, genetic susceptibility and progression can differ significantly, carrying crucial implications for precise diagnostics, clinical management, and efficacy of clinical drug trials. SNAP has caused wide interest in the dementia research community, because it is still unclear whether it represents distinct pathology separate from AD, or whether in some individuals, it could represent the earliest stage of AD. This debate has raised pertinent questions about the pathways to AD, the need for biomarkers, and the sensitivity of current biomarker tests. In this review, we discuss the biomarker and imaging trials that first recognised SNAP. We describe the pathological correlates of SNAP and comment on the different causes of neurodegeneration. Finally, we discuss the debate around the concept of SNAP, and further unanswered questions that are emerging. © 2017 Elsevier B.V. All rights reserved.

Amyloid deposition, tau aggregation and microglial activation in Alzheimer's disease: a PET study

Tau Imaging in Preclinical Alzheimer’s Disease

Imaging biomarkers in tauopathies

Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer’s disease (AD), frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. In AD, it has been shown that the density of hyperphosphorylated tau tangles correlates closely with neuronal dysfunction and cell death, unlike β-amyloid. Until now, diagnostic and pathologic information about tau deposition has only been available from invasive techniques such as brain biopsy or autopsy. The recent development of selective in-vivo tau PET imaging ligands including [18F]THK523, [18F]THK5117, [18F]THK5105 and [18F]THK5351, [18F]AV1451(T807) and [11C]PBB3 has provided information about the role of tau in the early phases of neurodegenerative diseases, and provided support for diagnosis, prognosis, and imaging biomarkers to track disease progression. Moreover, the spatial and longitudinal relationship of tau distribution compared with β - amyloid and other pathologies in these diseases can be mapped. In this review, we discuss the role of aggregated tau in tauopathies, the challenges posed in developing selective tau ligands as biomarkers, the state of development in tau tracers, and the new clinical information that has been uncovered, as well as the opportunities for improving diagnosis and designing clinical trials in the future.

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Tau imaging in neurodegenerative diseases

In vivo visualization of tau pathology

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In vivo visualization of tau pathology