论文信息 - Amyloid- and tau-PET imaging in a familial prion kindred

Amyloid- and tau-PET imaging in a familial prion kindred

Objective To study the in vivo binding properties of 18F-AV-1451 (tau-PET) and Pittsburgh compound B (PiB-PET) in a unique kindred with a familial prion disorder known to produce amyloid plaques composed of prion protein alongside Alzheimer disease (AD)–like tau tangles. Methods A case series of 4 symptomatic family members with the 12-octapeptide repeat insertion in the PRNP gene were imaged with 3T MRI, PiB-PET, and tau-PET in their fourth decade of life. Results There was significant neocortical uptake of the tau-PET tracer in all 4 familial prion cases. However, PiB-PET images did not demonstrate abnormally elevated signal in neocortical or cerebellar regions for any of the patients. Conclusions In vivo detection of molecular hallmarks of neurodegenerative diseases will be a prerequisite to well-conducted therapeutic trials. Understanding the in vivo behavior of these PET biomarkers in the setting of various neurodegenerative processes is imperative to their proper use in such trials and for research studies focused on the basic neurobiology of neurodegeneration. This study supports the high specificity of neocortical 18F-AV-1451 binding to AD-like tau and the lack of PiB binding to PrP plaques. It is uncertain how early in the disease course tau pathology appears in the brains of individuals who carry this PRNP gene mutation or how it evolves throughout the disease course, but future longitudinal 18F-AV-1451 imaging of symptomatic and asymptomatic individuals in this kindred will help address these uncertainties.

[1] David T. Jones,et al. In vivo 18F-AV-1451 tau PET signal in MAPT mutation carriers varies by expected tau isoforms , 2018, Neurology.

[2] Clifford R. Jack,et al. An autoradiographic evaluation of AV-1451 Tau PET in dementia , 2016, Acta Neuropathologica Communications.

[3] H. Kolb,et al. [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease , 2013, Alzheimer's & Dementia.

[4] C. Jack,et al. Clinical characterization of a kindred with a novel 12-octapeptide repeat insertion in the prion protein gene. , 2011, Archives of neurology.

[5] G. Schellenberg,et al. Familial prion disease with alzheimer disease‐like tau pathology and clinical phenotype , 2011, Annals of neurology.

[6] J. Mastrianni. The genetics of prion diseases , 2010, Genetics in Medicine.

[7] W. Klunk,et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B , 2004, Annals of neurology.

[8] K. Shimazu,et al. Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Sträussler-Scheinker syndrome P102L mutation complicated with dementia , 2002, Acta Neuropathologica.

[9] A. Delacourte,et al. Neurofibrillary tangles in Gerstmann-Sträussler-Scheinker syndrome with the A117V prion gene mutation , 1997, Journal of neurology, neurosurgery, and psychiatry.