Mathis CA, Klunk WE.
Imaging tau deposits in vivo: progress in viewing more of the proteopathy picture.
Neuron. 2013 Sep 18;79(6):1035-7.
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The latest entry in the roster of tau imaging agents is a 11C tracer: 11C-PBB3, based on a phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs) scaffold. These compounds are characterized by a π-electron-conjugated backbone with a specific extent ranging from 13 to19 Å that apparently allows binding to a broad range of AD and non-AD tau aggregates. Several PBB candidates underwent a thorough preclinical evaluation. While in-vitro autoradiographic studies in AD brain sections showed substantial non-selective binding, two-photon laser scanning fluorescence microscopy studies in a tau transgenic mouse model showed rapid clearance of the tracer with selective binding to tau tangles. Similar results were observed in microPET studies, showing higher PBB3 binding in the spinal cord of the same transgenic tau mouse model.
Preliminary clinical studies in three healthy control volunteers and three AD patients assessed with both 11C-PBB3 and 11C-PiB showed a different pattern of brain retention between the two tracers, suggesting that in vivo 11C-PBB3 binds selectively to tau. Notably, marked retention of 11C-PBB3 in the venous sinuses was also observed. A 11C-PBB3-PET study in a patient diagnosed with CBD showed tracer retention in the basal ganglia region, suggesting 11C-PBB3 might bind other, non-AD tau conformations.
The sensitivity and specificity of tau tracers for human tau pathology cannot be known until there have been a substantial number of imaged patients with autopsies and neuropathological diagnoses. Clinical diagnostic accuracy for non-Alzheimer's dementias, including corticobasal degeneration is poor (see references) and cannot be a substitute for autopsy. It will be difficult to devise tau ligands that do not also bind to Aβ; amyloid and it will take autopsy to prove this.
Shelley BP, Hodges JR, Kipps CM, Xuereb JH, Bak TH.
Is the pathology of corticobasal syndrome predictable in life?.
Mov Disord. 2009 Aug 15;24(11):1593-9.
Murray R, Neumann M, Forman MS, Farmer J, Massimo L, Rice A, Miller BL, Johnson JK, Clark CM, Hurtig HI, Gorno-Tempini ML, Lee VM, Trojanowski JQ, Grossman M.
Cognitive and motor assessment in autopsy-proven corticobasal degeneration.
Neurology. 2007 Apr 17;68(16):1274-83.
Doran M, du Plessis DG, Enevoldson TP, Fletcher NA, Ghadiali E, Larner AJ.
Pathological heterogeneity of clinically diagnosed corticobasal degeneration.
J Neurol Sci. 2003 Dec 15;216(1):127-34.
Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, Lai EC, Verny M, Ray-Chaudhuri K, McKee A, Jellinger K, Pearce RK, Bartko JJ.
Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study.
Neurology. 1997 Jan;48(1):119-25.
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