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@ARTICLE{Bernhardt:279350,
      author       = {Bernhardt, Alexander Maximilian and Rodríguez-Baz, Íñigo
                      and Aldecoa, Iban and Arranz, Javier and Arriola-Infante,
                      José Enrique and Maure-Blesa, Lucia and Carmona-Iragui,
                      Maria and Longen, Sebastian and Trossbach, Svenja Verena and
                      Giese, Armin and Matthias, Torsten and Benejam, Bessy and
                      Videla, Laura and Del Hoyo Soriano, Laura and Barroeta,
                      Isabel and Sanjuan, Aída and Fernández, Susana and
                      Vaqué-Alcázar, Lídia and Rozalem Aranha, Mateus and
                      Morcillo-Nieto, Alejandra O and Nübling, Georg and
                      Wagemann, Olivia and Stockbauer, Anna and Tondo, Mireia and
                      Bejanin, Alexandre and Lleó, Alberto and Alcolea, Daniel
                      and Molina-Porcel, Laura and Fortea, Juan and Levin,
                      Johannes},
      title        = {{A}lpha-synuclein co-pathology in {D}own
                      syndrome-associated {A}lzheimer's disease.},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {6},
      issn         = {1552-5260},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DZNE-2025-00727},
      pages        = {e70342},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Alzheimer Disease: pathology / Alzheimer Disease:
                      cerebrospinal fluid / alpha-Synuclein: cerebrospinal fluid /
                      Down Syndrome: pathology / Down Syndrome: complications /
                      Down Syndrome: cerebrospinal fluid / Female / Male / Middle
                      Aged / Aged / Amyloid beta-Peptides: cerebrospinal fluid /
                      Brain: pathology / Biomarkers: cerebrospinal fluid / tau
                      Proteins: cerebrospinal fluid / tau Proteins: blood / Adult
                      / Neurofilament Proteins: cerebrospinal fluid /
                      Neurofilament Proteins: blood / Alzheimer's disease (Other)
                      / Down syndrome (Other) / Lewy body pathology (Other) /
                      biomarker (Other) / neuropathology (Other) / seed
                      amplification assay (Other) / α‐synuclein (Other) /
                      alpha-Synuclein (NLM Chemicals) / Amyloid beta-Peptides (NLM
                      Chemicals) / Biomarkers (NLM Chemicals) / tau Proteins (NLM
                      Chemicals) / Neurofilament Proteins (NLM Chemicals)},
      cin          = {Clinical Research (Munich) / AG Levin / AG Simons},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015 / I:(DE-2719)1111016 /
                      I:(DE-2719)1110008},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 351 -
                      Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40528443},
      pmc          = {pmc:PMC12173960},
      doi          = {10.1002/alz.70342},
      url          = {https://pub.dzne.de/record/279350},
}