Abstract
PurposeIn vivo tau-PET tracer retention in the anterior temporal lobe of patients with semantic variant primary progressive aphasia (SV PPA) has consistently been reported. This is unexpected as the majority of these patients have frontotemporal lobar degeneration TDP (FTLD-TDP).MethodsWe conducted an in vitro [18F]AV1451 autoradiography binding study in five cases with a clinical diagnosis of SV PPA constituting the range of pathologies (i.e., three FTLD-TDP, one Alzheimer’s disease (AD), and one Pick’s disease (PiD)). Binding was compared with two controls without neurodegeneration, two typical AD, one corticobasal syndrome with underlying AD, and one frontotemporal dementia behavioral variant with FTLD-TDP. The effect of blocking with the authentic reference material and with the MAO-B inhibitor deprenyl was assessed. Immunohistochemistry was performed on adjacent cryosections.ResultsAbsence of specific [18F]AV1451 binding was observed for all three SV PPA FTLD-TDP cases. The absence of binding in controls as well as the successful blocking with authentic AV1451 in cases with tauopathy demonstrated specificity of the [18F]AV1451 signal for tau. The specific [18F]AV1451 binding was highest in AD, followed by PiD. This binding colocalized with the respective tau lesions and could not be blocked by deprenyl. Similar pilot findings were obtained with [18F]THK5351.ConclusionIn vitro autoradiography showed no [18F]AV1451 binding in SV PPA due to FTLD-TDP, while specific binding was present in SV PPA due to AD and PiD. The discrepancy between in vitro and in vivo findings remains to be explained. The discordance is not related to [18F]AV1451 idiosyncrasies as [18F]THK5351 findings were similar.
Highlights
The semantic variant of primary progressive aphasia (SV PPA), known as semantic dementia [1], is a languagebased neurodegenerative disorder which presents as a fluent, anomic aphasia with single-word comprehension problems and generally progressive loss of vocabulary and non-verbal knowledge [1, 2]
These findings are surprising since the vast majority of SV PPA patients have underlying TAR DNA-binding protein-43 (TDP-43) proteinopathy [5] and are not expected to show [18F]AV1451 binding in the anterior temporal lobe as the ligand has selectivity for tau over amyloid (29 fold) [7]
Considering [18F]AV1451 binding, the two typical Alzheimer’s disease (AD) cases showed the expected pattern, with strong cortical [18F]AV1451 binding, which was almost completely blocked in the presence of the authentic reference material (“cold” compound) and this result served as an internal positive control
Summary
The semantic variant of primary progressive aphasia (SV PPA), known as semantic dementia [1], is a languagebased neurodegenerative disorder which presents as a fluent, anomic aphasia with single-word comprehension problems and generally progressive loss of vocabulary and non-verbal knowledge [1, 2]. This pattern was observed in all 13 SV PPA cases who were amyloid-negative [14] Elevated binding in this peak region has been consistently observed with [18F]THK5351 across SV patients [13, 15, 16]. These findings are surprising since the vast majority of SV PPA patients have underlying TDP-43 proteinopathy [5] and are not expected to show [18F]AV1451 binding in the anterior temporal lobe as the ligand has selectivity for tau over amyloid (29 fold) [7]
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