Disease-related patterns of in vivo pathology in Corticobasal syndrome

Abstract

PurposeTo assess disease-related patterns of in vivo pathology in 11 patients with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild cognitive impairment (MCI) patients due to Alzheimer’s disease.MethodsWe assessed tau aggregates with [18F]AV1451 PET, amyloid-β depositions with [18F]AV45 PET, and volumetric microstructural changes with MRI. We validated for [18F]AV1451 standardised uptake value ratio (SUVRs) against input functions from arterial metabolites and found that SUVRs and arterial-derived distribution volume ratio (DVRs) provide equally robust measures of [18F]AV1451 binding.ResultsCBS patients showed increases in [18F]AV1451 SUVRs in parietal (P < 0.05) and frontal (P < 0.05) cortices in the affected hemisphere compared to healthy controls and in precentral (P = 0.008) and postcentral (P = 0.034) gyrus in the affected hemisphere compared to MCI patients. Our data were confirmed at the histopathological level in one CBS patient who underwent brain biopsy and showed sparse tau pathology in the parietal cortex co-localizing with increased [18F]AV1451 signal. Cortical and subcortical [18F]AV45 uptake was within normal levels in CBS patients. In parietal and frontal cortices of the most affected hemisphere we found also grey matter loss (P < 0.05), increased mean diffusivity (P < 0.05) and decreased fractional anisotropy (P < 0.05) in CBS patients compared to healthy controls and MCI patients. Grey matter loss and white matter changes in the precentral gyrus of CBS patients were associated with worse motor symptoms.ConclusionsOur findings demonstrate disease-related patterns of in vivo tau and microstructural pathology in the absence of amyloid-β, which distinguish CBS from non-affected individuals and MCI patients.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4104-2) contains supplementary material, which is available to authorized users.

Longitudinal changes in 18F‐THK5351 positron emission tomography in corticobasal syndrome

“…18 F‐AV1451 and 11 C‐PBB3 PET showed high uptake in the affected regions in CBS, but 18 F‐AV1451 showed difficulty in detecting the deposits of 4‐repeat tau using autoradiography and has off‐target binding to several molecules, such as monoamine oxidase A and neuromelanin , which are not related to tau pathology. 11 C‐PBB3 PET studies have been conducted in only single cases , and possible off‐target binding of 11 C‐PBB3 remains unclear.…”

“…Another possibility is that any changes in 18 F-THK5351 retention are masked by 18 F-THK5351 binding to physiological MAO-B-containing cells in these brain areas [9]. 18 F-AV1451 [5][6][7] and 11 C-PBB3 [3,12] PET showed high uptake in the affected regions in CBS, but 18 F-AV1451 showed difficulty in detecting the deposits of 4-repeat tau using autoradiography [13][14][15] and has off-target binding to several molecules, such as monoamine oxidase A [16] and neuromelanin [17], which are not related to tau pathology. 11 C-PBB3 PET studies have been conducted in only single cases [3,12], and possible off-target binding of 11 C-PBB3 remains unclear.…”

“…features include intracellular fibrillary tangles of tau protein; in CBD and PSP, tau is in its 4-repeat isoform, whereas in Alzheimer's disease the tangles are composed of both 3-and 4-repeat isoforms. Several recent studies have attempted to visualize these pathological changes in CBS [3][4][5][6][7]. In one of these, 18 F-THK5351 positron emission tomography (PET) demonstrated distinctive spatial patterns of radiotracer binding in patients with CBS [4].…”

Validation of the Movement Disorder Society Criteria for the Diagnosis of 4‐Repeat Tauopathies

“…In conclusion, the concept of 4R‐tauopathies imposes clear advantages for clinical diagnosis and research. In the light of potential tauopathy‐specific interventions, the early clinical recognition of 4R‐tauopathies is crucial and will require more research, especially into 4R‐tauopathy–specific in vivo biomarkers, such as biofluid proteins and tauopathy positron emission tomography ligands …”

Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment

“…A recent study also links tau burden quantified by [ 18 F]AV-1451 to neurodegeneration, specifically longitudinal brain atrophy (Das et al, 2018). For example, patients diagnosed with corticobasal syndrome show retention increases in frontal and parietal cortices compared to those with MCI due to AD (Niccolini et al, 2018). For example, patients diagnosed with corticobasal syndrome show retention increases in frontal and parietal cortices compared to those with MCI due to AD (Niccolini et al, 2018).…”