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The effect of APOE ɛ4 in Alzheimer’s disease biomarkers in Down syndrome
Author(s) -
Vilaplana Eduard,
Videla Laura,
CarmonaIragui Maria,
Benejam Bessy,
Barroeta Isabel,
Fernandez Susana,
Altuna Miren,
Pegueroles Jordi,
Montal Victor,
Bejanin Alexandre,
Iulita M. Florencia,
Valldeneu Sílvia,
GonzálezOrtiz Sofía,
Muñoz Laia,
Camacho Valle,
Videla Sebastián,
Alcolea Daniel,
Blesa Rafael,
Lleó Alberto,
Clarimon Jordi,
Fortea Juan
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.042889
Subject(s) - apolipoprotein e , biomarker , medicine , asymptomatic , oncology , cohort , dementia , allele , population , gastroenterology , disease , biology , genetics , environmental health , gene
Background The APOE ɛ4 allele is the main genetic risk factor for sporadic Alzheimer’s disease (AD). However, its influence on AD in Down syndrome (DS) has received less attention. Our main objective was to study the effect of the APOE ɛ4 allele in AD biomarkers in a population‐based cohort of adults with DS. Method Cross‐sectional study. We selected adults with DS and euploid healthy controls from Hospital de Sant Pau, Barcelona. We included all participants with known APOE genotype and at least one biomarker measured in: plasma, CSF or neuroimaging (MRI, FDG‐PET or Florbetapir‐PET). DS participants were classified into asymptomatic and symptomatic (prodromal or AD dementia). Aβ1‐42, total‐tau and NfL levels were measured in plasma using SIMOA and in CSF using Lumipulse. We extracted mean FDG‐PET SUVR (Landau), we measured the Centiloid score for Florbetapir‐PET and the adjusted hippocampal volumes from MRI. Subjects were classified into APOE ɛ4 carriers and non‐carriers. We compared age of symptoms onset between APOE ɛ4 carriers vs non‐carriers, and we fitted within‐group local regression models to compare the association of biomarkers with age between groups. Result We included 325 individuals with DS (214 asymptomatic and 111 symptomatic) and 239 controls (Table 1). When comparing age at diagnosis, subjects with DS harboring at least an APOE ɛ4 allele were two years younger than non‐carriers (51.1 vs 53.2, p=0.08). We then compared biomarker trajectories between APOE ɛ4 carriers and non‐carriers. As displayed in Figure 1, subjects with DS harboring an APOE ɛ4 allele showed earlier decreases in CSF Aß1‐42 and increases in Florbetapir Centiloid. APOE ɛ4 carriers showed a steeper decline in brain metabolism (FDG‐PET SUVR) in the fifth decade compared to APOE ɛ4 non‐carriers. No differences were found in total‐tau and NfL in CSF or plasma, or in hippocampal volume trajectories. Conclusion APOE ɛ4 allele may influence the onset of AD‐related symptoms in DS. This effect might be due to earlier amyloid deposition and brain hypometabolism. The presence of APOE ɛ4 does not seem to have an effect on total‐tau, NfL or hippocampal volume. In conclusion, these results provide further insight on the relationship between APOE ɛ4 and AD pathophysiological processes.