Tau accumulates differently in four subtypes of Alzheimer's disease

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Heterogeneity in Alzheimer's disease (AD) has been reported on the basis of clinical, neuropathological, and neuroimaging data. However, most of the indices, including cerebral atrophy evaluated using magnetic resonance imaging and amyloid β (Aβ) accumulation detected using positron emission tomography (PET), lack sensitivity, and specificity for categorization.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>Herein, we used a novel PET ligand for tau to estimate the differential distribution of tau in the subtypes of AD.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients with posterior cortical atrophy (PCA; <jats:italic>n</jats:italic> = 3), frontal variant of AD (FAD; <jats:italic>n</jats:italic> = 1), logopenic variant primary progressive aphasia (LPPA; <jats:italic>n</jats:italic> = 2), typical AD (TAD; <jats:italic>n</jats:italic> = 6), and healthy controls (HC; <jats:italic>n</jats:italic> = 12) were studied. Aβ and tau accumulation were evaluated using [<jats:sup>11</jats:sup>C]PiB and [<jats:sup>11</jats:sup>C]PBB3, respectively.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Amyloid β accumulation was confirmed in all PCA, FAD, LPPA, and TAD cases. Tau accumulation was dominantly high in the occipital lobes in the PCA, strikingly high in the frontal lobes in the FAD, and moderately high in the angular gyrus of the dominant hemisphere in the LPPA. Tau accumulation in TAD cases was significantly higher than age‐dependent tau accumulation in HC in these subtype‐specific regions as well as in AD signature regions. Glucose utilization was reversely correlated with PBB3 accumulation in the subtype‐specific regions.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Tau accumulates differently in the four subtypes of AD, suggesting that tau pathology may be closely associated with unique clinical features.</jats:p></jats:sec>