Tau Positron Emission Tomography Imaging in Degenerative Parkinsonisms

Abstract

In recent years, several radiotracers that selectively bind to pathological tau proteins have been developed. Evidence is emerging that binding patterns of in vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD) patients closely resemble the distribution patterns of known neurofibrillary tangle pathology, with the extent of tracer binding reflecting the clinical and pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has clearly revealed cortical tau burden with a distribution pattern distinct from AD and increased cortical binding within the LBD spectrum. In progressive supranuclear palsy, the globus pallidus and midbrain have shown increased binding most prominently. Tau PET patterns in patients with corticobasal syndrome are characterized by asymmetrical uptake in the motor cortex and underlying white matter, as well as in the basal ganglia. Even in the patients with multiple system atrophy, which is basically a synucleinopathy, ¹⁸F-flortaucipir, a widely used tau PET tracer, also binds to the atrophic posterior putamen, possibly due to off-target binding. These distinct patterns of tau-selective radiotracer binding in the various degenerative parkinsonisms suggest its utility as a potential imaging biomarker for the differential diagnosis of parkinsonisms.

Keywords: Tau; parkinsonism; positron emission tomography.

Figure 1.

Structures of tau-selective radiotracers.

Figure 2.

Different nigral ¹⁸F-flortaucipir binding in PD and PSP. A: Compared to the controls, ¹⁸F-flortaucipir SUVR values in the substantia nigra were 13% lower in PD patients and 10% higher in PSP patients. B: A demonstration of different nigral ¹⁸F-flortaucipir binding in a control subject and patients with PD and PSP. HC: healthy controls, PD: Parkinson’s disease, PSP: progressive supranuclear palsy, SUVR: standardized uptake value ratio.

Figure 3.

Group-averaged ¹⁸F-flortaucipir PET images in various degenerative parkinsonisms. In LBD, ¹⁸F-flortaucipir PET shows an increasing pattern of cortical binding with the advancement of the disease. In addition, different degenerative parkinsonisms show distinct patterns of ¹⁸F-flortaucipir binding; compared to the controls, lower binding has been observed in the substantia nigra in PD, in contrast to higher binding in PSP, as well as higher binding in the globus pallidus and dentate nucleus in PSP, asymmetrically increased binding in the basal ganglia, substantia nigra and white matter underlying the motor cortex in CBS, and asymmetrically increased binding in the putamen in MSA. Color bars represent SUVR values. LBD: Lewy body diseases, HC: healthy controls, PDNC: Parkinson’s disease with normal cognition, PDMCI: Parkinson’s disease with mild cognitive impairment, PDD: Parkinson’s disease with dementia, DLB: dementia with Lewy bodies, AD: Alzheimer’s disease, PSP: progressive supranuclear palsy, CBS: corticobasal syndrome, MSA: multiple system atrophy, C/I: contralateral or ipsilateral to the clinically more affected side, SUVR: standardized uptake value ratio, PET: positron emission tomography.