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@INPROCEEDINGS{RodrguezBaz:283150,
      author       = {Rodríguez-Baz, Íñigo and Bernhardt, Alexander M and
                      Aldecoa, Iban and Arranz, Javier and Arriola-Infante, José
                      Enrique and Maure-Blesa, Lucía and Carmona-Iragui, Maria
                      and Longen, Sebastian and Trossbach, Svenja Verena and
                      Giese, Armin and Matthias, Torsten and Benejam, Bessy and
                      Videla, Laura and Hoyo, Laura Del and Barroeta, Isabel and
                      Hernandez, Aida Sanjuan and Fernandez, Susana and
                      Vaqué-Alcázar, Lídia and Aranha, Mateus Rozalem 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, Laura and Fortea, Juan and Levin, Johannes},
      title        = {{A}lpha-{S}ynuclein {P}athology in {D}own
                      {S}yndrome-{A}ssociated {A}lzheimer's {D}isease: {I}nsights
                      from {S}eed {A}mplification {A}ssay and {N}europathology},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {S2},
      issn         = {1552-5260},
      reportid     = {DZNE-2026-00046},
      pages        = {e106390},
      year         = {2025},
      abstract     = {Down syndrome (DS) is a genetic cause of Alzheimer's
                      disease (AD), with virtually all individuals developing AD
                      pathology by their fourth decade due to Amyloid Precursor
                      Protein (APP) gene overexpression. In addition to amyloid
                      beta (Aβ) plaques and hyperphosphorylated tau (p-Tau)
                      aggregates, DS-associated AD (DSAD) often includes
                      α-synuclein (αSyn) aggregates, contributing to Lewy body
                      pathology (LBP). The αSyn Seed Amplification Assay (SAA) in
                      cerebrospinal fluid (CSF) enables the in vivo detection of
                      misfolded αSyn. While αSyn-SAA has revealed αSyn
                      pathology in autosomal dominant $(6\%-11\%)$ and sporadic
                      $(21\%-45\%)$ AD, its role in DSAD remains unexplored. This
                      study investigates αSyn-SAA positivity in DSAD, linking in
                      vivo findings to fluid biomarkers and neuropathology.We
                      analyzed CSF of 270 adults with DS from the DABNI and AD21
                      cohorts by αSyn-SAA, encompassing asymptomatic and
                      symptomatic AD stages (prodromal/dementia). Additional
                      biomarkers included CSF Aβ1-42/1-40, CSF and plasma
                      p-Tau181 and neurofilament light chain (NfL) levels.
                      Neuropathological evaluations in 19 brain donors, including
                      5 with antemortem CSF, assessed AD neuropathology and LBP.As
                      shown in Table 1, αSyn-SAA positivity was observed in
                      $9.2\%$ of participants, consistent across age groups
                      (Figure 1) and cognitive stages. Symptomatic
                      αSyn-SAA-positive individuals exhibited significantly
                      higher plasma NfL levels compared to αSyn-SAA-negative
                      individuals (31.0 vs. 21.1 pg/mL, p = 0.027).
                      Neuropathological analysis revealed LBP in $47\%$ of cases,
                      with the amygdala and olfactory bulb being the most
                      frequently affected regions (Table 2). Among the five donors
                      with antemortem CSF, the only αSyn-SAA-positive case
                      corresponded to an individual with severe neocortical
                      LBP.This study examines the relationship between LBP and
                      DSAD, identifying a prevalence of αSyn-SAA positivity
                      comparable to autosomal dominant AD but lower than sporadic
                      AD. A potential association was noted between severe
                      neocortical LBP and αSyn seeding activity, while age and
                      cognitive status did not significantly influence positivity
                      rates. Misfolded αSyn was detectable from early ages in
                      individuals with DS. Further research is required to
                      elucidate the mechanisms underlying LBP in DSAD, assess its
                      clinical impact on cognitive and motor symptoms, and explore
                      relationships with other biomarkers.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      keywords     = {Humans / Biomarkers: cerebrospinal fluid / Male / Female /
                      Alzheimer Disease: cerebrospinal fluid / Alzheimer Disease:
                      pathology / alpha-Synuclein: cerebrospinal fluid / Amyloid
                      beta-Peptides: cerebrospinal fluid / Down Syndrome:
                      cerebrospinal fluid / Down Syndrome: pathology / Middle Aged
                      / tau Proteins: cerebrospinal fluid / Aged / Adult /
                      Neurofilament Proteins: cerebrospinal fluid / Cohort Studies
                      / Peptide Fragments: cerebrospinal fluid / Biomarkers (NLM
                      Chemicals) / alpha-Synuclein (NLM Chemicals) / Amyloid
                      beta-Peptides (NLM Chemicals) / tau Proteins (NLM Chemicals)
                      / Neurofilament Proteins (NLM Chemicals) / Peptide Fragments
                      (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)1 / PUB:(DE-HGF)16},
      pubmed       = {pmid:41500202},
      doi          = {10.1002/alz70856_106390},
      url          = {https://pub.dzne.de/record/283150},
}