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@INPROCEEDINGS{ZaragozaBallester:283079,
      author       = {Zaragoza-Ballester, Pablo and Nuscher, Briggitte and
                      Alcolea, Daniel and Fernández-León, Álex and
                      Rodríguez-Baz, Íñigo and Bejanin, Alexandre and Vera,
                      Elena and Vaqué-Alcázar, Lídia and Sala, Isabel and
                      Gómez-Grande, Adolfo and Lleo, Alberto and Fortea, Juan and
                      Camacho, Valle and Haass, Christian and Morenas-Rodriguez,
                      Estrella},
      title        = {{A}ssociation between soluble {TREM}2, {APOE} genotype,
                      {A}lzheimer's copathology and disease evolution in dementia
                      with {L}ewy bodies},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {Suppl 1},
      issn         = {1552-5260},
      reportid     = {DZNE-2025-01486},
      pages        = {e102529},
      year         = {2025},
      abstract     = {APOEε4 is a genetic risk factor for both Alzheimer's
                      Disease (AD) and dementia with Lewy bodies (DLB).
                      TREM2-dependent microglial activation is considered
                      protective in AD and has been proposed to interact with APOE
                      in this context. Since DLB often exhibits Alzheimer's
                      copathology, we investigate the interplay between TREM2
                      response, APOEε4 carriage and Alzheimer's co-pathology, and
                      its influence on disease evolution in DLB.We measured
                      cerebrospinal fluid (CSF) cleaved soluble TREM2 (cTREM2), as
                      a marker of TREM2-dependent microglial response, core AD
                      biomarkers and determine APOEε4 carriage in 76 DLB patients
                      (prodromal DLB [prodDLB], n = 39; DLB-dementia, n = 37).
                      Forty one patients additionally underwent
                      [18F]Florbetapir-PET (FBP-PET). We quantified cTREM2 by an
                      in-house MSD-based immunoassay; core AD biomarkers (Aβ42,
                      t-tau, p-tau181), by ELISA; and FBP-PET uptake, by standard
                      uptake value ratio (SUVr). We stratified patients according
                      to the A/T classification. Clinical follow-up (>1 year) was
                      available for 69 patients.APOEε4 carriers had lower cTREM2
                      levels compared to non-carriers in prodDLB
                      (3.72±1.79vs.6.83±2.25ng/mL, p-value=0.0005, Figure 1).
                      Furthermore, APOEε4 carriage itself was associated with
                      lower cTREM2 levels in prodDLB (β(carriers)=-0.42,
                      p-value=0.025) independently of AD core biomarkers.
                      Conversely, APOEe4 carriage did not impact cTREM2 levels in
                      DLB-dementia. cTREM2 levels across A-/+ and T-/+ DLB groups
                      are represented in Figure 1. In prodDLB, higher cTREM2
                      levels were associated with higher Aβ42 (β=0.77,
                      p-value=0.0002) and p-tau181 levels (β=0.612,
                      p-value=0.002). In DLB-dementia, cTREM2 levels were
                      associated only with p-tau181 (β=0.58, p-value=0.0001).
                      Additionally, higher cTREM2 levels were associated with
                      lower FBP-PET SUVr in prodDLB (β=-1.71, p-value=0.04).
                      Notably, higher sTREM2 levels at baseline in prodDLB were
                      related to a smaller subsequent longitudinal decrease in
                      MMSE scores (β=1.11, p-value=0.01). No significant
                      relationship was observed between baseline cTREM2 at a
                      DLB-dementia stage and subsequent cognitive decline
                      (β=-0.3, p-value=0.5).APOEε4 carriage attenuates the
                      TREM2-dependent microglial response in prodromal DLB, as
                      reflected by lower CSF cTREM2 levels. Elevated cTREM2 levels
                      in the prodromal phase are associated with slower cognitive
                      decline, suggesting a protective role of microglial
                      activation during early disease stages. These findings
                      suggest an early modulation of TREM2-driven microglial
                      response by APOEε4 which influences DLB progression.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      keywords     = {Humans / Male / Female / Aged / Biomarkers: cerebrospinal
                      fluid / Apolipoprotein E4: genetics / Alzheimer Disease:
                      genetics / Alzheimer Disease: cerebrospinal fluid /
                      Alzheimer Disease: pathology / Lewy Body Disease: genetics /
                      Lewy Body Disease: cerebrospinal fluid / Lewy Body Disease:
                      diagnostic imaging / Lewy Body Disease: pathology / Membrane
                      Glycoproteins: cerebrospinal fluid / Receptors, Immunologic
                      / Amyloid beta-Peptides: cerebrospinal fluid /
                      Positron-Emission Tomography / tau Proteins: cerebrospinal
                      fluid / Middle Aged / Aged, 80 and over / Biomarkers (NLM
                      Chemicals) / TREM2 protein, human (NLM Chemicals) /
                      Apolipoprotein E4 (NLM Chemicals) / Membrane Glycoproteins
                      (NLM Chemicals) / Receptors, Immunologic (NLM Chemicals) /
                      Amyloid beta-Peptides (NLM Chemicals) / tau Proteins (NLM
                      Chemicals)},
      cin          = {AG Haass},
      ddc          = {610},
      cid          = {I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      pubmed       = {pmid:41436355},
      pmc          = {pmc:PMC12727221},
      doi          = {10.1002/alz70855_102529},
      url          = {https://pub.dzne.de/record/283079},
}