Alpha-synuclein co-pathology in Down syndrome-associated Alzheimer's disease

INTRODUCTION: Alpha-synuclein (alpha Syn) seed amplification assay (SAA) enables in vivo study of alpha Syn but remains underexplored in Down syndrome-associated Alzheimer's disease (DSAD). METHODS: We analyzed alpha Syn-SAA in cerebrospinal fluid (CSF) from 270 adults with Down syndrome, from...

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Detalles Bibliográficos
Autores: Bernhardt, AM, Rodríguez-Baz, I, Aldecoa, I, Arranz, J, Arriola-Infante, JE, Maure-Blesa, L, Carmona-Iragui, M, Longen, S, Trossbach, SV, Giese, A, Matthias, T, Benejam, B, Videla, L, Soriano, LD, Barroeta, I, Sanjuan, A, Fernandez, S, Vaqué-Alcázar, L, Aranha, MR, Morcillo-Nieto, AO, Nübling, G, Wagemann, O, Stockbauer, A, Tondo, M, Bejanin, A, Lleó, A, Alcolea, D, Molina-Porcel, L, Fortea, J, Levin, J
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p19756
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19756
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
biomarker
Down syndrome
Lewy body pathology
neuropathology
seed amplification assay
alpha-synuclein
Descripción
Sumario:INTRODUCTION: Alpha-synuclein (alpha Syn) seed amplification assay (SAA) enables in vivo study of alpha Syn but remains underexplored in Down syndrome-associated Alzheimer's disease (DSAD). METHODS: We analyzed alpha Syn-SAA in cerebrospinal fluid (CSF) from 270 adults with Down syndrome, from the Down Alzheimer Barcelona Neuroimaging Initiative and from the AD21 cohort from the Department of Neurology at the University Hospital, Ludwig Maximilian University of Munich, Germany. Neuropathological examinations were conducted in 19 brain donors (five with ante mortem CSF). Participants were classified as asymptomatic or symptomatic (prodromal/dementia) Alzheimer's disease (AD). CSF A beta 1-42/1-40, CSF and plasma p-Tau181, and neurofilament light chain (NfL) levels were measured. Neuropathological evaluations assessed AD neuropathological changes and Lewy body pathology (LBP). RESULTS: Alpha Syn-SAA was positive in 9.2% of cases, independent of age or cognitive status. Symptomatic alpha Syn-positive cases exhibited higher plasma NfL levels than alpha Syn-negative cases (31 vs 21 pg/mL, p = 0.027). LBP was observed in 47% of necropsies. The individual with severe neocortical LBP was alpha Syn-SAA-positive. DISCUSSION: These findings highlight LBP prevalence in DSAD but suggest current SAA may fail to detect limited alpha Syn deposition. Highlights center dot alpha Syn-SAA positivity in DSAD is 9.2%, similar to ADAD but lower than sporadic AD. center dot Misfolded alpha Syn was detectable from early ages in individuals with DS. center dot Positivity rates did not vary with age or clinical status in DS. center dot Plasma NfL levels are higher in symptomatic alpha Syn-SAA positive versus negative cases. center dot CSF alpha Syn seeding activity was associated with high neocortical LBP at necropsy.

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