18F]PI2620 tau deposition increases along the Alzheimer’s disease continuum in Down Syndrome and in presence of amyloid

Abstract

AbstractBackgroundDown’s syndrome (DS) is currently considered a genetic form of Alzheimer’s disease (AD). People with DS develop early‐onset AD due to an extra copy of the amyloid precursor protein gene, present on chromosome 21. Thus, DS is a unique model to study AD pathophysiology. We aimed to study the neurofibrillary tau burden in adults with DS using the second‐generation Tau PET tracer [18F]PI‐2620 and assess its relationship with amyloid PET.MethodCross‐sectional study. We included 46 subjects: 18 euploid subjects without cognitive impairment and 16 asymptomatic DS, 4 DS with prodromal AD and 8 DS with AD dementia. All subjects underwent dynamic [18F]PI‐2620 PET/CT, [18F]Flutemetamol amyloid PET/CT and T1w‐MRI scans. PET images were co‐registered to the corresponding T1w‐MRI and intensity normalized by the mean value in the reference region (whole cerebellum for [18F]Flutemetamol and inferior cerebellar cortex for [18F]PI‐2620). For amyloid PET, the mean of the composite region (frontal, temporal, parietal, and cingulate) was calculated and transformed into Centiloid units. [18F]PI‐2620 tracer retention was quantified in region of interest (ROIs) corresponding to individual anatomical definitions of Braak stages I‐II, III‐IV and V‐VI. ANOVA was used to test differences between clinical diagnoses. To assess the relationship between amyloid and tau, vertex‐wise analysis was performed using the PETSurfer toolbox of Freesurfer.ResultThe pattern of tau deposition in symptomatic DS included typical AD areas (i.e., temporal and parietal lobe, precuneus; Fig1). Differences in [18F]‐PI2620 uptake along the AD continuum in DS were statistically significant in the three Braak staging ROIs only between asymptomatic DS and demented DS, although a trend was observed between controls and demented DS (Fig2). The vertex‐wise regression showed a relationship between local tau burden and global amyloid deposition in widespread areas, but especially in typical AD ones (Fig3; FWE‐corrected p<0.05).Conclusion[18F]PI‐2620 PET presented high affinity to tau aggregates in symptomatic DS subjects, and presented similar deposition as in sporadic AD. Tau PET deposition measured by [18F]PI‐2620 increased along the AD continuum in DS and was mainly present in subjects with high amyloid burden.