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000283079 037__ $$aDZNE-2025-01486
000283079 041__ $$aEnglish
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000283079 1001_ $$aZaragoza-Ballester, Pablo$$b0
000283079 1112_ $$aAlzheimer’s Association International Conference$$cToronto$$d2025-07-27 - 2025-07-31$$gAAIC 25$$wCanada
000283079 245__ $$aAssociation between soluble TREM2, APOE genotype, Alzheimer's copathology and disease evolution in dementia with Lewy bodies
000283079 260__ $$c2025
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000283079 520__ $$aAPOEε4 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.
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000283079 650_7 $$2NLM Chemicals$$aBiomarkers
000283079 650_7 $$2NLM Chemicals$$aTREM2 protein, human
000283079 650_7 $$2NLM Chemicals$$aApolipoprotein E4
000283079 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000283079 650_7 $$2NLM Chemicals$$aReceptors, Immunologic
000283079 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000283079 650_7 $$2NLM Chemicals$$atau Proteins
000283079 650_2 $$2MeSH$$aHumans
000283079 650_2 $$2MeSH$$aMale
000283079 650_2 $$2MeSH$$aFemale
000283079 650_2 $$2MeSH$$aAged
000283079 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000283079 650_2 $$2MeSH$$aApolipoprotein E4: genetics
000283079 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000283079 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000283079 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000283079 650_2 $$2MeSH$$aLewy Body Disease: genetics
000283079 650_2 $$2MeSH$$aLewy Body Disease: cerebrospinal fluid
000283079 650_2 $$2MeSH$$aLewy Body Disease: diagnostic imaging
000283079 650_2 $$2MeSH$$aLewy Body Disease: pathology
000283079 650_2 $$2MeSH$$aMembrane Glycoproteins: cerebrospinal fluid
000283079 650_2 $$2MeSH$$aReceptors, Immunologic
000283079 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000283079 650_2 $$2MeSH$$aPositron-Emission Tomography
000283079 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000283079 650_2 $$2MeSH$$aMiddle Aged
000283079 650_2 $$2MeSH$$aAged, 80 and over
000283079 7001_ $$0P:(DE-HGF)0$$aNuscher, Briggitte$$b1
000283079 7001_ $$aAlcolea, Daniel$$b2
000283079 7001_ $$aFernández-León, Álex$$b3
000283079 7001_ $$aRodríguez-Baz, Íñigo$$b4
000283079 7001_ $$aBejanin, Alexandre$$b5
000283079 7001_ $$aVera, Elena$$b6
000283079 7001_ $$aVaqué-Alcázar, Lídia$$b7
000283079 7001_ $$aSala, Isabel$$b8
000283079 7001_ $$aGómez-Grande, Adolfo$$b9
000283079 7001_ $$aLleo, Alberto$$b10
000283079 7001_ $$aFortea, Juan$$b11
000283079 7001_ $$aCamacho, Valle$$b12
000283079 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b13$$udzne
000283079 7001_ $$0P:(DE-2719)2812759$$aMorenas-Rodriguez, Estrella$$b14
000283079 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz70855_102529$$gVol. 21 Suppl 1, no. Suppl 1, p. e102529$$nSuppl 1$$pe102529$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025
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