School of Medicine Publications and Presentations

Regional patterns of pathological tau accumulation in sporadic early-onset Alzheimer’s disease: Longitudinal tau-PET in the LEADS Cohort

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The longitudinal progression of tau pathology in sporadic early-onset Alzheimer’s disease (EOAD, age-at-onset<65) has not been well established and may be key to its understanding and treatment. We utilized in vivo PET imaging to characterize regional patterns of pathological tau accumulation in the Longitudinal Early-onset Alzheimer’s Disease Study (LEADS), an ongoing, large-sample, multi-site cohort.


[18F]Flortaucipir tau-PET was acquired 75-105min post-injection in 277 amyloid-PET-positive patients with sporadic EOAD and 90 healthy controls (Table 1). Patients had mild cognitive impairment (CDR-SB = 0.5-4, n = 206) or mild dementia (CDR-SB = 4.5-8, n = 71) at baseline. Longitudinal tau-PET was collected in 126 patients (2-4 scans/subject, 1.3 ± 0.4 years apart). Tau-PET SUVRs were calculated in 72 FreeSurfer-defined regions referenced against inferior cerebellar gray matter, and SUVRs were W-scored within-region to adjust for age and sex associations in controls (control W-score mean = 0, SD = 1). Baseline tau-PET W-score differences between patients and controls were assessed using linear regression. Linear mixed-effects models were used to calculate tau-PET W-score change rates among EOAD patients.


Tau-PET was significantly elevated in EOAD patients at baseline in every region examined (p<0.05, FDR-corrected), with highest tau-PET signal in lateral prefrontal, parietal, and posterior cingulate cortices bilaterally, and relative sparing of primary cortices (Figure 1a). In longitudinal analyses, tau-PET increased significantly in 69/72 regions (p<0.05, FDR-corrected; Figure 1b), and regions with higher tau-PET at baseline had faster prospective accumulation rates on average (r = 0.47, p<0.0001; Figure 2). Exceptions were noted in posterior cingulate and parietal association regions, which had high tau-PET at baseline but comparatively slow accumulation; and in anterior prefrontal and occipital regions with low-to-moderate tau-PET at baseline yet rapid accumulation.


Tau pathology is present throughout cortex by the mild dementia stage in EOAD and is still accumulating globally, especially in anterior prefrontal and occipital cortices. Parietal association regions have high baseline tau but slower-than-expected prospective accumulation, suggesting these regions are early pathological foci that plateau early in the clinical disease stage.


University of Texas Health Science - San Antonio.

© 2023 the Alzheimer's Association.

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Alzheimer's & dementia : the journal of the Alzheimer's Association



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