CSF α-synuclein SAA detects Lewy body dementia with 95% sensitivity in multicenter cohortResearchers find new test spots Lewy body dementia

medRxiv Published April 24, 2026 Study authors: Jourdan, O.; Duchiron, M.; Torrent, J.; Turpinat, C.; Mondesert, E.; Busto, G.; Morchikh, M.; Dornad… DOI ↗ Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain

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Key Takeaway

Consider CSF α-synuclein SAA for detecting Lewy body dementia, noting its high sensitivity and specificity in this cohort.

This multicenter, prospective cohort study included 398 patients from memory clinics in Montpellier, Nimes, and Perpignan. The study assessed the diagnostic performance of CSF α-synuclein seed amplification assay (SAA) for distinguishing Lewy body dementia (LBD) from patients without LBD or Alzheimer's disease (AD).

In the LBD group, 19 out of 20 patients were SAA-positive (95.0%). In the AD group, 32 out of 203 patients were SAA-positive (15.8%). The SAA demonstrated a sensitivity of 95% and a specificity of 93.5% for distinguishing LBD from patients without LBD or AD.

In the entire cohort, SAA-positive patients had lower MMSE scores (p<0.01), a lower CSF Aβ42/40 ratio (p<0.01), and elevated plasma GFAP (p<0.05) compared to SAA-negative patients. In the AD subgroup, no significant differences were observed between SAA-positive and SAA-negative patients, except for a lower CSF Aβ42/40 ratio in SAA-positive patients (p<0.01).

Safety and tolerability data were not reported. Key limitations include the observational design, which cannot establish causation, and the lack of reported follow-up duration. The practice relevance is that SAA demonstrates good diagnostic capabilities for detecting LBD and confirms notable synuclein co-pathology in AD, highlighting the value of integrating SAA into routine neurodegenerative disease assessment.

This study tested a new method called the alpha-synuclein seed amplification assay (SAA) to help distinguish Lewy body dementia (LBD) from Alzheimer’s disease and other conditions. Researchers worked with 398 patients from memory clinics in Montpellier, Nimes, and Perpignan, using spinal fluid and blood samples along with cognitive assessments.

The SAA test was positive in 19 out of 20 patients with LBD, showing high sensitivity for detection. It also identified alpha-synuclein pathology in about 16% of patients with Alzheimer’s disease. The test showed strong diagnostic performance, with 95% sensitivity and 93.5% specificity for distinguishing LBD from patients without LBD or Alzheimer’s.

Patients who tested positive on the SAA had lower cognitive scores and other biological changes, such as lower CSF Aβ42/40 ratios and higher plasma GFAP. However, the study did not report safety data, and it was an observational cohort study, so it shows associations, not cause-and-effect.

The main reason to be careful is that this is an early, practice-relevant finding from a single clinical setting. It suggests the SAA could improve diagnosis, but more research is needed before it becomes routine.

What this means for you:

A new test shows promise for detecting Lewy body dementia, but it is still being studied and not yet standard care.

Study Details

Study typeCohort

Sample sizen = 398

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

Objectives: To evaluate the diagnostic performance of the -synuclein seed amplification assay (SAA) and characterize the impact of -synuclein co-pathology on cognitive and biological profiles in routine clinical practice. Methods: We included 398 patients from the prospective multicenter ALZAN cohort recruited from memory clinics in Montpellier, Nimes, and Perpignan. All participants underwent CSF and blood sampling with measurement of CSF biomarkers (A{beta}42/40, tau, ptau181) and plasma biomarkers (A{beta}42/40, ptau181, ptau217, GFAP, NfL). Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Clinical diagnoses were independently confirmed by two senior neurologists. Syn status was determined by SAA (RT-QuIC). Results: Of 398 patients, 19 out of 20 patients with Lewy body dementia (LBD) (95.0%) and 32 out of 203 patients with AD (15.8%) were SAA+. SAA-positivity presented a sensitivity of 95% and a specificity of 93.5% for distinguishing LBD from patients without LBD or AD. In the entire cohort, SAA+ patients showed lower MMSE scores (p<0.01), lower CSF A{beta}42/40 ratio (p<0.01), and elevated plasma GFAP (p<0.05). Within the AD group, no significant differences in CSF or blood biomarkers were observed between SAA+ and SAA- patients. Within the AD subgroup, no significant differences in CSF or blood biomarkers were observed between SAA+ and SAA- patients, except for a lower CSF A{beta}42/40 ratio in SAA+ patients (p<0.01). Interpretation: SAA demonstrates good diagnostic capabilities for detecting LBD and confirms notable Syn co-pathology in AD. This study highlights the limitations of routine CSF and emerging blood biomarkers in capturing Syn pathology and the value of integrating SAA into routine neurodegenerative disease assessment.

CSF α-synuclein SAA detects Lewy body dementia with 95% sensitivity in multicenter cohortResearchers find new test spots Lewy body dementia

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CSF α-synuclein SAA detects Lewy body dementia with 95% sensitivity in multicenter cohortResearchers find new test spots Lewy body dementia

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