Tau positron emission tomographic imaging in aging and early Alzheimer disease

Abstract

Objective Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer’s disease (AD), staging and monitoring of disease progression, and development of disease modifying therapies. Methods We acquired tau positron emission tomography (PET) using 18F T807 (AV1451), and amyloid-β PET using 11C Pittsburgh Compound B (PIB) in older clinically normal individuals, and symptomatic patients with mild cognitive impairment or mild AD dementia. Results We found abnormally high cortical 18F T807 binding in patients with mild cognitive impairment and AD dementia compared to clinically normal controls. Consistent with the neuropathology literature, the presence of elevated neocortical 18F T807 binding particularly in the inferior temporal gyrus was associated with clinical impairment. The association of cognitive impairment was stronger with inferior temporal 18F T807 than with mean cortical 11C PIB. Regional 18F T807 was correlated with mean cortical 11C PiB among both impaired and control subjects. Interpretation These findings suggest that 18F T807 PET could have value as a biomarker that reflects both the progression of AD tauopathy and the emergence of clinical impairment.

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials

“…Tau PET can also be used for Braak staging of participants. Data suggest that most amyloid-positive patients with AD are in Braak stage VI, while the majority of amyloid-negative patients with AD had Braak stages of III or lower [41,44]. Across AD and CN participants, tau PET measures also significantly correlate with cerebrospinal fluid (CSF) levels of amyloid and tau [39].…”

“…Specifically, patients with AD show significant tau PET tracer uptake in the temporal, parietal, and frontal lobes, while the primary sensory/motor cortices are relatively spared [30,[39][40][41][42][43][44]. Tau in the inferior temporal lobe is associated with increased amyloid deposition on PET, as well as greater cognitive impairment and disease severity in AD [41,44]. Tau PET can also be used for Braak staging of participants.…”

“…In the high-tau MCI, stage I commonly observes binding in the anterior, inferior, and lateral temporal lobes. In the dementia stages the tau deposition in the previously involved areas becomes denser and tau binding is also observed in the other associations fields like the parietal and frontal lobes as seen in the figure cingulate, and fusiform, entorhinal, and parahippocampal gyri [30,40,41,44]. As the MCI stage is quite heterogeneous, patients can demonstrate a full range of Braak stages, from I to VI [44].…”

Elevated 18 F-AV-1451 PET tracer uptake detected in incidental imaging findings

“…[1][2][3] Human studies evaluating AV-1451 tracer retention in aging and Alzheimer disease (AD) have indicated that in vivo binding patterns parallel existing neuropathologic staging of tau. 4,5 Despite the applicability of this ligand for imaging tau in aging and dementia, in certain conditions tracer binding might complicate image interpretation. Pathologic studies have found AV-1451 also showing retention unrelated to tau; this off-target binding may reflect iron deposition, neuromelanin, or vascular factors.…”

“…2,3 An outbreak of ZIKV infection in New Caledonia occurred in 2014 with 1,380 confirmed cases within a population of 263,000. 4 We report 2 cases of myasthenia gravis (MG) with prior ZIKV infection.…”