Determination of diagnostic cutoffs for tau‐PET: A preliminary study based on tau and beta‐amyloid PET measurements

Background Alzheimer’s Disease (AD) is characterized by abnormal concentration of beta‐amyloid (AB) and tau proteins which can be assessed using positron emission tomography (PET). Currently, no relative standardized uptake value (rSUV) cutoff defines an AD diagnostic tau‐PET, and the literature is mainly focused on defining a cutoff per Braak stage which correlates with disease progression. Method In this study, we used tau‐rSUV values of cortical and subcortical regions to define three diagnostic cutoffs for tau‐PET using age‐ and gender‐matched data (average age = 72.9 ± 7.36 y.o.; gender = 56.1% male) of AD and mild cognitive impairment (MCI) patients, and cognitively normal (CN) subjects from the Alzheimer's Disease Neuroimaging Initiative. The diagnostic groups were: 1) CN (n = 54) vs MCI and AD (nMCI = 46, nAD = 14); 2) AB negative CN (n = 35) vs AB positive MCI and AD (nMCI = 26, nAD = 12); and 3) AB negative (n = 87: 65 CN, 20 MCI, 2 AD) vs AB positive (n=73: 36 CN, 26 MCI, 12 AD). Tau‐rSUV values were normalized for each region volume using the inferior cerebellum as a reference. Regions that provided significant differences in rSUV values between the diagnostic groups were considered to compute a composite tau‐rSUV value. Then, for each case, a cutoff value was defined using the composite tau‐rSUV value that maximizes the chi‐square statistic value with the highest significance. Result For the case CN vs (MCI+AD) the diagnostic cutoff tau‐rSUV value was 1.10 (Qui‐square = 19.9; p‐value < 0.001); for AB negative CN vs AB positive MCI and AD the cutoff tau‐rSUV was 1.16 (Qui‐square = 30.3; p‐value < 0.001); while in AB negative vs AB positive the cutoff tau‐rSUV was 1.21 (Qui‐square = 31.0; p‐value < 0.001). Conclusion Our diagnostic cutoff tau‐rSUV values are within the interval of values [1.19 to 1.34] previously reported [1]–[3]. The results highlight that the cutoff values are related to AB status: if the latter is unknown, the cutoff may be more restricted; while the third cutoff indicates that AB negative MCI and AD subjects already show the presence of tau protein.