Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions

Abstract

Most neurodegenerative disorders are associated with aggregated protein deposits. In the case of Alzheimer disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Aβ-PET imaging has already been approved for clinical use and is being used in clinical trials of anti-Aβ therapies both for patient recruitment and as an outcome measure. These studies have shown that Aβ accumulation is a protracted process that can extend for more than 2 decades before the onset of clinical AD. This Review describes how in vivo brain imaging of Aβ pathology has revolutionized the evaluation of patients with clinical AD by providing robust and reproducible statements of global or regional brain Aβ burden and enabling the monitoring of disease progression. The role of selective tau imaging is discussed, focusing on how longitudinal tau and Aβ imaging studies might reveal the various effects (sequential and/or parallel, independent and/or synergistic) of these proteins on progression, cognition and other disease-specific biomarkers of neurodegeneration. Finally, imaging studies are discussed in the context of elucidating the respective roles of Aβ and tau in AD and in advancing our understanding of the relationship and/or interplay between these two proteinopathies.

Interval timing is disrupted in female 5xFAD mice: An indication of altered memory processes

“…Alzheimer's disease (AD) is characterized by the progressive hippocampal and neocortical neurodegeneration that results in cognitive, affective, and motor disruptions (Buchman & Bennett, 2011;McKhann et al, 2011;Pini et al, 2016;Rosenberg, Nowrangi, & Lyketsos, 2015;Scheltens et al, 2016). Senile plaque and neurofibrillary tangle aggregations, as well as loss of basal forebrain cholinergic neurons, are found in the brains of AD patients (Auld, Kornecook, Bastianetto, & Quirion, 2002;Frankó, Joly, & Alzheimer's Disease Neuroimaging Initiative, 2013;Villemagne, Doré, Burnham, Masters, & Rowe, 2018) collectively contributing to dysfunctions in synaptic transmission (Baker-Nigh et al, 2015;Bloom, 2014;Hampel et al, 2018;Koss et al, 2016;Piccini et al, 2005;Willén, Sroka, Takahashi, & Gouras, 2017). The resultant decline in cognitive functions of AD patients is not limited to episodic memory but also encompasses executive functions and attention, starting in the early stages of the disease (Buckner, 2004;Kirova, Bays, & Lagalwar, 2015;Stopford, Thompson, Neary, Richardson, & Snowden, 2012;Storandt, 2008).…”

Progression of logopenic aphasia to frontotemporal dementia in an amyloid β‐negative and 18F‐THK‐5351‐positive patient

“…The limitation of this study is that our case may have FTLD-TDP or FTLD-Pick because 18 F-THK-5351 binds to monoamine oxidase B as well as to paired helical filament tau. 6 In fact, monoamine oxidase B activity is greatly increased in the frontal and temporal poles of individuals with Pick's disease (Sparks et al 1991) (File S3). Based on a recent report, this is not necessarily the case with 18 F-THK-5351, which specifically binds to 4R tau.…”

Aβ and the dementia syndrome: Simple versus complex perspectives

“…Recent studies show that in vivo tau PET imaging has a better correlation with clinical AD stage than amyloid PET imaging, while 18 F‐FDG PET imaging is a better clinical biomarker of disease development than tau PET imaging . The promising results regarding monitoring of disease progression need to be confirmed in larger prospective studies and further evidence of the clinical validity and utility of 18 F‐FDG PET imaging is needed .…”