ArticleAnnals of neurology2025
Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts.
Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Improving the clinical trial landscape for patients with atypical variants of Alzheimer's disease: a call to action.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Thalamic nuclei insights into Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Real-world implementation of lecanemab and donanemab in an Italian memory center: a 1-year experience.Alzheimer's research & therapy · 2026Observational
- Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Tau topography subtypes account for clinical heterogeneity and longitudinal trajectories in early-onset Alzheimer's disease.Brain communications · 2026Article
- Tablet-based Cognitive Assessment Tool (TabCAT) in a multisite study of early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Alterations of the brain functional organization in young-onset Alzheimer's disease: Is it a matter of "time"?Journal of Alzheimer's disease : JAD · 2025Article
- Alpha-synuclein deposition patterns in Alzheimer's disease: association with cortical amyloid beta and variable tau load.Acta neuropathologica · 2025Article
- Identification of patients receiving amyloid-targeting therapies in observational studies using amyloid PET trajectories: Insights from LEADS.Alzheimer's & dementia (Amsterdam, Netherlands)Article
- Sex and ethnicity in early-onset Alzheimer's disease biomarkers and global function.Alzheimer's & dementia (Amsterdam, Netherlands)Article
- Anti-amyloid immunotherapy and brain volume trajectories in early-onset versus late-onset Alzheimer's disease.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Abstract
objectiveEarly-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large-scale comparative studies.
methodsThree hundred ninety-nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition.
resultsThe amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74-82) than in ADNI (71%, 95% CI = 67-75, p = 0.02). Lower Mini-Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid-positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD.
interpretationDifferences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236-248.
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