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001     279350
005     20250713001445.0
024 7 _ |a 10.1002/alz.70342
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024 7 _ |a 1552-5260
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024 7 _ |a 1552-5279
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037 _ _ |a DZNE-2025-00727
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Bernhardt, Alexander Maximilian
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245 _ _ |a Alpha-synuclein co-pathology in Down syndrome-associated Alzheimer's disease.
260 _ _ |a Hoboken, NJ
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|b Wiley
336 7 _ |a article
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520 _ _ |a Alpha-synuclein (αSyn) seed amplification assay (SAA) enables in vivo study of αSyn but remains underexplored in Down syndrome-associated Alzheimer's disease (DSAD).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).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.These findings highlight LBP prevalence in DSAD but suggest current SAA may fail to detect limited αSyn deposition.αSyn-SAA positivity in DSAD is 9.2%, similar to ADAD but lower than sporadic AD. Misfolded αSyn was detectable from early ages in individuals with DS. Positivity rates did not vary with age or clinical status in DS. Plasma NfL levels are higher in symptomatic αSyn-SAA positive versus negative cases. CSF αSyn seeding activity was associated with high neocortical LBP at necropsy.
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650 _ 7 |a Alzheimer's disease
|2 Other
650 _ 7 |a Down syndrome
|2 Other
650 _ 7 |a Lewy body pathology
|2 Other
650 _ 7 |a biomarker
|2 Other
650 _ 7 |a neuropathology
|2 Other
650 _ 7 |a seed amplification assay
|2 Other
650 _ 7 |a α‐synuclein
|2 Other
650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a Biomarkers
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650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a Neurofilament Proteins
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: cerebrospinal fluid
|2 MeSH
650 _ 2 |a alpha-Synuclein: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Down Syndrome: pathology
|2 MeSH
650 _ 2 |a Down Syndrome: complications
|2 MeSH
650 _ 2 |a Down Syndrome: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Biomarkers: cerebrospinal fluid
|2 MeSH
650 _ 2 |a tau Proteins: cerebrospinal fluid
|2 MeSH
650 _ 2 |a tau Proteins: blood
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Neurofilament Proteins: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Neurofilament Proteins: blood
|2 MeSH
700 1 _ |a Rodríguez-Baz, Íñigo
|0 0000-0003-3039-9115
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700 1 _ |a Aldecoa, Iban
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700 1 _ |a Arranz, Javier
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700 1 _ |a Arriola-Infante, José Enrique
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700 1 _ |a Maure-Blesa, Lucia
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700 1 _ |a Carmona-Iragui, Maria
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700 1 _ |a Longen, Sebastian
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700 1 _ |a Trossbach, Svenja Verena
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700 1 _ |a Giese, Armin
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700 1 _ |a Matthias, Torsten
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700 1 _ |a Benejam, Bessy
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700 1 _ |a Videla, Laura
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700 1 _ |a Del Hoyo Soriano, Laura
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700 1 _ |a Barroeta, Isabel
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700 1 _ |a Sanjuan, Aída
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700 1 _ |a Fernández, Susana
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700 1 _ |a Vaqué-Alcázar, Lídia
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700 1 _ |a Rozalem Aranha, Mateus
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700 1 _ |a Morcillo-Nieto, Alejandra O
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700 1 _ |a Nübling, Georg
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700 1 _ |a Wagemann, Olivia
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700 1 _ |a Stockbauer, Anna
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700 1 _ |a Tondo, Mireia
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700 1 _ |a Bejanin, Alexandre
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700 1 _ |a Lleó, Alberto
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700 1 _ |a Alcolea, Daniel
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700 1 _ |a Molina-Porcel, Laura
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700 1 _ |a Fortea, Juan
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700 1 _ |a Levin, Johannes
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773 _ _ |a 10.1002/alz.70342
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