ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Association of CSF α-synuclein seed amplification assay positivity with disease progression and cognitive decline: A longitudinal Alzheimer's Disease Neuroimaging Initiative study.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed.
- CSF α-synuclein seed amplification assay positivity identifies a distinct soluble amyloid-β profile linked to fibrillar amyloid burden and structural neurodegeneration.Research square · 2026Article
- Deep learning-based MRI analysis reveals Lewy body co-pathology accelerates brain aging in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- CSF alpha-Synuclein Seed Amplification Assay results in routine clinically collected samples.Journal of Parkinson's disease · 2026Article
- A Systematic Comparison of Alpha-Synuclein Seed Amplification Assays for Increasing Reproducibility.Annals of clinical and translational neurology · 2026Review
- ATNIVS biomarker heterogeneity in real-world patients receiving lecanemab.The journal of prevention of Alzheimer's disease · 2026Article
- Co-pathologies and biological processes beyond amyloid-beta and tau in people with Alzheimer's disease: Evidence from clinical cohort studies.Journal of internal medicine · 2026Review
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Seed Amplification Assays for Parkinson's Disease: A Review of α-Synuclein Assays in Body Fluids and Tissues.Journal of neurochemistry · 2026Review
- Beyond Lipidation: CSF APOE4 Protein Burden, Not HDL Subclass, Drives Tau Associations in APOE4 Alzheimer's Disease.Research square · 2026Article
- Alpha-synuclein co-pathology amplifies amyloid-driven tau accumulation across Braak stages without modifying tau-cognition associations.bioRxiv : the preprint server for biology · 2026Article
- Consistency of Serial CSF alpha-Synuclein Seed Amplification Assay Results in the Parkinson's Progression Marker Initiative.medRxiv : the preprint server for health sciences · 2026Article
- Towards biomarker-based diagnosis of Parkinson disease.Nature reviews. Neurology · 2026Review
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Detection of alpha-synuclein seeding activity in tear fluid in patients with Parkinson's disease.NPJ Parkinson's disease · 2026Article
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Combining plasma biomarkers, clinical parameters, and neuroimaging features for differential diagnosis of Parkinson's disease and atypical parkinsonian syndromes: a multidimensional modeling approach.Frontiers in aging neuroscience · 2026Article
- Neural basis of motor symptoms in Alzheimer's disease: role of regional tau burden and cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Plasma tau biomarkers are distinctly associated with tau tangles and decreased with Lewy body pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Increased cerebrospinal fluid and plasma apoE glycosylation is associated with reduced levels of Alzheimer's disease biomarkers.Alzheimer's research & therapy · 2025Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
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Abstract
introductionCerebrospinal fluid (CSF) α-synuclein (α-syn) seed amplification assay (SAA) is a sensitive and specific tool for detecting Lewy body co-pathology in Alzheimer's disease.
methodsA total of 1637 cross-sectional and 407 longitudinal CSF samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were tested with SAA. We examined longitudinal dynamics of amyloid beta (Aβ), α-syn seeds, and phosphorylated tau181 (p-tau181), along with global and domain-specific cognition in stable SAA+, stable SAA-, and those who converted to SAA+ from SAA-.
resultsSAA+ individuals had faster cognitive decline than SAA-, notably in mild cognitive impairment, and presented with earlier symptom onset. SAA+ conversion was associated with CSF Aβ42 positivity but did not impact the progression of either CSF Aβ42 or CSF p-tau181 status. CSF Aβ42, p-tau181, and α-syn SAA were all strong predictors of clinical progression, particularly CSF Aβ42. In vitro, CSF α-syn SAA kinetic parameters were associated with participant demographics, clinical profiles, and cognitive decline. DISCUSSION: These results highlight the interplay between amyloid and α-syn and their association with disease progression. HIGHLIGHTS: Seed amplification assay (SAA) positivity was associated with greater cognitive decline and earlier symptom onset. Thirty-four Alzheimer's Disease Neuroimaging Initiative (ADNI) individuals progressed from SAA- to SAA+, that is, ≈ 5% conversion. SAA conversion was associated with amyloid beta (Aβ) pathology and greater cognitive decline. SAA status did not impact the progression of either CSF Aβ42 or phosphorylated tau181 biomarkers. Change in clinical diagnosis was associated with both Alzheimer's disease biomarkers and SAA. SAA kinetic parameters were associated with clinical features and progression.
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