Tau positron emission tomographic imaging in aging and early Alzheimer disease - PubMed (original) (raw)

doi: 10.1002/ana.24546. Epub 2015 Dec 15.

Keith A Johnson 1 2 3 4 5, Aaron Schultz 1 4 6, J Alex Becker 1 3, Jorge Sepulcre 1 3 5 6, Dorene Rentz 2 4 5, Elizabeth Mormino 2 4, Jasmeer Chhatwal 2 4 5, Rebecca Amariglio 2 4 5, Kate Papp 2 4 5, Gad Marshall 2 4 5, Mark Albers 2 5, Samantha Mauro 1 3, Lesley Pepin 1 3, Jonathan Alverio 1 3, Kelly Judge 1 3, Marlie Philiossaint 1 3, Timothy Shoup 1 3, Daniel Yokell 1 3 5, Bradford Dickerson 1 2 5 6, Teresa Gomez-Isla 2 5, Bradley Hyman 2 5, Neil Vasdev 1 3 5, Reisa Sperling 2 4 5 6

Affiliations

Tau positron emission tomographic imaging in aging and early Alzheimer disease

Keith A Johnson et al. Ann Neurol. 2016 Jan.

Abstract

Objective: Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease-modifying therapies.

Methods: We acquired tau positron emission tomography (PET) using (18)F T807 (AV1451), and amyloid-β PET using (11)C 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 (18)F 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 (18)F T807 binding particularly in the inferior temporal gyrus was associated with clinical impairment. The association of cognitive impairment was stronger with inferior temporal (18)F T807 than with mean cortical (11)C PIB. Regional (18)F T807 was correlated with mean cortical (11)C PiB among both impaired and control subjects.

Interpretation: These findings suggest that (18)F T807 PET could have value as a biomarker that reflects both the progression of AD tauopathy and the emergence of clinical impairment.

© 2015 American Neurological Association.

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Conflict of interest statement

Potential Conflict of Interests: AS, RB, JAB, JS, DR, EM, JC, RA, KP, GM, SM, LP, JA, KJ, MP, TS, DY, and TG have no competing interests.

Figures

Figure 1

Figure 1

Cortical patterns of 18F T807 binding. Coronal 18F T807 PET images (top row) and whole-brain surface renderings of SUVR (second row) from 3 normal (CN) and 4 impaired (2 MCI and 2 AD dementia) participants. Top row A. A 71 year-old CN with low Aβ by PiB PET (DVR=1.0) had low, non-specific 18F T807 binding in cortex, consistent with a Braak Stage less than III/IV. B. A 74 year-old CN with high Aβ (DVR=1.2) with 18F T807 binding in inferior temporal cortex, left>right, consistent with Braak Stage III/IV. C. A 79 year-old CN, high Aβ (DVR=1.8) had binding in inferior temporal neocortex, consistent with Braak Stage of III/IV. B and C show focally intense subcortical uptake that is likely due to off-target binding (see Discussion). D–G. Cognitively impaired participants all with high Aβ and with successively greater levels of cortical 18F T807 binding successively involving temporal, parietal, frontal and occipital cortices. Second row: 18F T807 SUVR calculated at vertices (see Methods) indicating the extent of cortical binding, with left hemisphere views (lateral, inferior, superior, medial) at left. The 52 year-old AD dementia patient (G) showed confluent 18F T807 binding that is nearly pancortical, sparing only portions of primary cortex and consistent with Braak Stage V/VI. MMSE= mini-mental state exam PiB= Pittsburgh Compound B DVR= distribution volume ratio, mean cortical SUVR= standardized uptake value, cerebellar reference Dx= classification (CN, clinically normal; MCI, mild cognitive impairment; AD mild AD dementia) PET Braak= Estimate of Braak Stages is based on the anatomic pattern of T807 binding assessed visually and quantitatively in regions and full volume data.

Figure 2

Figure 2

Cortical distribution of T807 binding, contrast between the combined MCI/AD group (N=19) and the CN group (N=56; threshold p< 10^−5).

Figure 3

Figure 3

Regional T807 binding according to diagnostic group. T807 standardized uptake value radio (SUVR) in regions-of-interest (ROI) by diagnostic group (CN, circles; MCI, triangles; AD, squares) and amyloid status (high Aβ, red, = PiB DVR 1.2 or greater), showing range, mean, interquartile range. t-test: *p<0.01, **p<0.001

Figure 4

Figure 4

A – F. Correlations of Tau pathology measured with 18F T807 and Aβ pathology measured with 11C PiB with Mini-Mental State Examination, CDR Sum of Boxes, and Logical Memory 2. Clinically normal subjects are represented with circles, MCI with triangles, and AD with squares; red indicates high Aβ (PiB DVR >1.2) and black low Aβ (PiB DVR ≤1.2). Spearman correlations (rho) are given below for each PET measure versus MMSE, CDR SB, or LM. A. MMSE vs. Inferior temporal T807 [Table: see text] B. MMSE vs. mean cortical PiB DVR [Table: see text] C. CDR SB vs. Inferior temporal T807 [Table: see text] D. CDR SB vs. mean cortical PiB DVR [Table: see text] E. LM vs. Inferior temporal T807 [Table: see text] F. LM vs. mean cortical PiB DVR [Table: see text]

Figure 5

Figure 5

Correlations of tau pathology measured with inferior temporal 18F T807 and Aβ pathology measured with mean cortical 11C PiB. Clinically normal subjects are represented with circles, MCI with triangles, and AD with squares; red indicates high Aβ (PiB DVR >1.2) and black low Aβ (PiB DVR ≤1.2). Separate linear fit lines (dashed for CN, solid for MCI/AD) are shown to aid inspection. ρ = Spearman’s Rho. [Table: see text]

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