Regional tau deposition in probable Alzheimer’s disease using C-11-PBB3-PET: a voxel-wise statistical analysis

Ziel/Aim C-11-pyridinyl-butadienyl-benzothiazole3 (PBB3) PET has the potential to quantify accumulation of tau deposits in Alzheimer’s disease (AD). Here we compared the regional tau load between cognitively normal, probable AD and patients with suspected non-AD pathophysiology (SNAP) using PBB3-PET.

Methodik/Methods 23 patients (M: 12; F: 11; age: 65.5 ± 6.6 y) with decreased recent memory were examined using PBB3-PET. PiB-PET was available for 17, FDG-PET for 16, and CSF protein levels for 11 patients. CSF biomarkers were considered positive based on Aβ (< 550 ng/L) and t-total (> 350 ng/L). All PET images were analyzed using SPM. FDG-PET positivity was defined by comparing each scan to a cognitively normal group. The adaptive template method was used for amyloid quantification. PiB-PET positivity was defined by comparing the normalized cross-correlation between templates and the spatially normalized image. Based on the A/T/N system (1), patients were classified as probable AD (A + N +), SNAP (A-N +) and cognitively normal (A-N-). The PBB3-PET load was compared among the groups using VOI-based quantification of target-to-cerebellum SUVRs. The clusters surviving at p < 0.05 (FWE corrected, k < 100) were considered as VOIs.

Ergebnisse/Results 7 patients were identified as probable AD, 9 SNAP and 7 cognitively normal. Significantly higher PBB3 binding was observed in the probable AD group compared to the normal patients in the posterior cingulate (1.73 ± 0.11 vs. 1.35 ± 0.07), temporal (1.09 ± 0.05 vs. 0.87 ± 0.05) and frontal region (1.01 ± 0.04 vs. 0.79 ± 0.06). Compared to the SNAP group, probable AD patients had a slightly increased PBB3 uptake over the superior parietal (0.73 ± 0.05 vs. 0.55 ± 0.05), middle cingulate (0.95 ± 0.08 vs. 0.69 ± 0.06) and posterior cingulate (0.85 ± 0.04 vs. 0.66 ± 0.05).

Schlussfolgerungen/Conclusions Statistical voxel-wise analysis effectively showed group differences in PBB3-PET signal, suggesting that PBB3-PET is an effective surrogate parameter for tau load and disease severity.

• Literatur/References

• 1 Jack CR, Jr.. , Bennett DA, Blennow K. , et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease.. Alzheimer's & dementia: The Journal of the Alzheimer's Association. 2018; 14 (4): 535-62.