Highly specific amyloid and tau PET ligands for ATN classification in suspected Alzheimer's disease patients

This study aims to accurately classify ATN profiles using highly specific amyloid and tau PET ligands and MRI in patients with cognitive impairment and suspected Alzheimer's disease (AD). It also aims to explore the relationship between quantified amyloid and tau deposition and cognitive function.

Twenty-seven patients (15 women and 12 men; age range: 64-81 years) were included in this study. Amyloid and tau PET scans were performed using ¹⁸F-NAV4694 and ¹⁸F-MK6240, respectively. For each patient, amyloid and tau PET images were visually assessed and classified as either amyloid-positive or amyloid-negative, and as ¹⁸F-MK6240 Braak stage 0 (tau-negative) or Braak stages I-VI (tau-positive). Voxel-based morphometry of three-dimensional T1-weighted MRI was used to evaluate neurodegeneration. Amyloid and tau depositions were quantified using the Centiloid scale and standardized uptake value ratio (SUVR), respectively. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE).

Patients were categorized into seven ATN profiles. Six patients (22%) exhibited a normal AD biomarker profile, 15 patients (56%) fell within the Alzheimer's continuum, and 14 patients (52%) were diagnosed with AD. Additionally, six patients (22%) displayed non-AD pathological changes. Positive and negative findings of amyloid and tau PET were concordant in 24 patients (89%). Among the 14 patients diagnosed with AD, the Centiloid scale for amyloid deposition did not show a significant negative correlation with MMSE scores (r = 0.269, p = 0.451). In contrast, the SUVR for tau deposition in the neocortex exhibited a significant negative correlation (r = -0.689, p = 0.014), while tau deposition in the mesial temporal region did not show a significant correlation (r = 0.158, p = 0.763).

Highly specific amyloid and tau PET scans, along with MRI, can be utilized to accurately classify ATN profiles in patients with cognitive impairment and suspected AD. The discordance in amyloid and tau PET findings in three patients allowed for a more precise AD diagnosis. Furthermore, tau PET imaging provided insight into the propagation of tau deposition in the neocortex beyond the mesial temporal region, which is associated with cognitive decline.