Amyloid and tau‐PET in early‐onset AD: Baseline data from the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS)

Abstract

INTRODUCTIONWe aimed to describe baseline amyloid‐beta (Aβ) and tau‐positron emission tomograrphy (PET) from Longitudinal Early‐onset Alzheimer's Disease Study (LEADS), a prospective multi‐site observational study of sporadic early‐onset Alzheimer's disease (EOAD).METHODSWe analyzed baseline [18F]Florbetaben (Aβ) and [18F]Flortaucipir (tau)‐PET from cognitively impaired participants with a clinical diagnosis of mild cognitive impairment (MCI) or AD dementia aged < 65 years. Florbetaben scans were used to distinguish cognitively impaired participants with EOAD (Aβ+) from EOnonAD (Aβ−) based on the combination of visual read by expert reader and image quantification.RESULTS243/321 (75.7%) of participants were assigned to the EOAD group based on amyloid‐PET; 231 (95.1%) of them were tau‐PET positive (A+T+). Tau‐PET signal was elevated across cortical regions with a parietal‐predominant pattern, and higher burden was observed in younger and female EOAD participants.DISCUSSIONLEADS data emphasizes the importance of biomarkers to enhance diagnostic accuracy in EOAD. The advanced tau‐PET binding at baseline might have implications for therapeutic strategies in patients with EOAD.HIGHLIGHTS 72% of patients with clinical EOAD were positive on both amyloid‐ and tau‐PET. Amyloid‐positive patients with EOAD had high tau‐PET signal across cortical regions. In EOAD, tau‐PET mediated the relationship between amyloid‐PET and MMSE. Among EOAD patients, younger onset and female sex were associated with higher tau‐PET.

Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early‐onset Alzheimer's disease

“…The quantitative threshold used for amyloid PET positivity is a global SUVR ≥ 1.18, extracted from a PET‐only pipeline. The full details of all PET methods and thresholds are described elsewhere in this special issue 29 …”

“…Volumetric measures for MRI and regional and composite SUVR values for amyloid and tau PET were downloaded from LONI and extracted using Freesurfer 7.1. Details on the methods to extract these values are described previously and elsewhere in this special issue 26,29 …”

“…33 The resulting gray matter maps were normalized and smoothed with a 10-mm Gaussian kernel, which yielded gray matter density (GMD) images to be used in imaging analysis. The downloaded PET scans were coregistered to the corresponding MRI scan from the same visit, normalized to Montreal Neurological Institute (MNI) space using transformation parameters from VBM MRI segmentation, and rescaled to MRI-defined reference regions 26,29 (amyloid PET to whole cerebellum and tau PET to inferior cerebellar gray matter) using SPM via MATLAB. Quality control was conducted on all final processed MRI and PET images.…”

“…Details on the methods to extract these values are described previously and elsewhere in this special issue. 26,29 F I G U R E 1 Analysis workflow. A visual representation of groups used for each analysis.…”

Default mode network tau predicts future clinical decline in atypical early Alzheimer’s disease

“…At baseline, all patients underwent neuroimaging sessions involving structural MRI, FTP PET, and amyloid (either 18 F-Florbetaben [FBB] or 11 C-Pittsburgh Compound B [PiB]) PET scans. Aβ positivity was determined by a combination of visual read and mean amyloid PET signal extracted from a cortical composite region of interest according to previously published procedures [46][47][48] . Determination of tau and neurodegeneration positivity was conducted by visual read using internal methods similar to published work [49][50][51] .…”