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

Bernhardt, Alexander Maximilian ; Rodríguez‐Baz, Íñigo ; Aldecoa, Iban; Arranz, Javier; Arriola‐Infante, José Enrique; Maure‐Blesa, Lucia; Carmona‐Iragui, Maria; Longen, Sebastian; Trossbach, Svenja Verena; Giese, Armin; Matthias, Torsten; Benejam, Bessy; Videla, Laura; del Hoyo Soriano, Laura; Barroeta, Isabel; Sanjuan, Aída; Fernández, Susana; Vaqué‐Alcázar, Lídia; Rozalem Aranha, Mateus; Morcillo‐Nieto, Alejandra O.; Nübling, Georg; Wagemann, Olivia; Stockbauer, Anna; Tondo, Mireia; Bejanin, Alexandre; Lleó, Alberto; Alcolea, Daniel; Molina‐Porcel, Laura; Fortea, Juan und Levin, Johannes (2025): Alpha‐synuclein co‐pathology in Down syndrome‐associated Alzheimer's disease. In: Alzheimer's & Dementia, Bd. 21, Nr. 6, e70342

Abstract

INTRODUCTION

Alpha-synuclein (αSyn) seed amplification assay (SAA) enables in vivo study of αSyn but remains underexplored in Down syndrome-associated Alzheimer's disease (DSAD).

METHODS

We analyzed αSyn-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 Aβ1-42/1-40, 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

ΑSyn-SAA was positive in 9.2% of cases, independent of age or cognitive status. Symptomatic αSyn-positive cases exhibited higher plasma NfL levels than αSyn-negative cases (31 vs 21 pg/mL, p = 0.027). LBP was observed in 47% of necropsies. The individual with severe neocortical LBP was αSyn-SAA-positive.

DISCUSSION

These findings highlight LBP prevalence in DSAD but suggest current SAA may fail to detect limited αSyn deposition.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Klinikum der LMU München > Neurologische Klinik und Poliklinik mit Friedrich-Baur-Institut
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198