IntroductionAmyloid-β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and Alzheimer's disease (AD), respectively. Interactions between Aβ and tau accumulations and their influence on clinical features, however, are still unclear.MethodsAssociations among clinical symptoms, gray-matter volume, regional tau, and Aβ deposition assessed by positron emission tomography with [11C]pyridinyl-butadienyl-benzothiazole 3 (PBB3) and [11C]Pittsburgh compound-B (PiB), were evaluated in 17 AD, 9 mild cognitive impairment due to AD, and 28 PiB(−)-cognitive healthy controls (HCs).ResultsHigh tau burden was associated with aging and low-level education in PiB(−)-HC and AD-spectrum groups, and with high Aβ burden and low-level education in all subjects. It was not Aβ but tau accumulation that showed significant associations with cognitive performance even in PiB(−)-HC.DiscussionThe present study indicated aging and low-level education after Aβ would be enhancers for tau pathology, associated with neurodegeneration and cognitive impairment in healthy and diseased elderly individuals.

Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We aimed to assess the efficacy and safety of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ATTRv amyloidosis with polyneuropathy. MethodsThis multi-country, multi-centre, open-label extension (OLE) trial enrolled patients at 43 sites in 19 countries as of 24 September 2018. Patients were eligible if they had completed the phase 3 APOLLO (randomised, double-blind, placebo-controlled [2:1], 18-month study) or phase 2 OLE (single-arm, 24-month study) parent studies and tolerated the study drug. Eligible patients from APOLLO (APOLLO-patisiran [received patisiran during APOLLO] and APOLLO-placebo [received placebo during APOLLO] groups) and the phase 2 OLE (phase 2 OLE patisiran group) studies enrolled in this Global OLE trial and receive patisiran 0•3 mg/kg by intravenous infusion every 3 weeks for up to 5 years. Efficacy assessments include measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress. Patients included in the current efficacy analyses are those who had completed 12-month efficacy assessments as of the data cut-off. Safety analyses included all patients who received ≥1 dose of patisiran up to the data cut-off. The Global OLE is ongoing with no new enrolment, and current findings are based on the 12-month interim analysis. The study is registered with ClinicalTrials.gov, NCT02510261.

Background [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP. Objectives To explore the usefulness of [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients. Methods We assessed 13 PSP patients and 13 age‐matched healthy control subjects. Individuals negative for amyloid β PET with [ 11 C]Pittsburgh compound B underwent clinical scoring, MR scans, and [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3/PET. Results There were significant differences in binding potential for [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3 between PSP patients and healthy control subjects ( P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl‐butadienyl‐benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues. Conclusions Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [ 11 C]pyridinyl‐butadienyl‐benzothiazole 3/PET potentially provides a neuroimaging‐based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.