Alvar Agustí, Albert Compte, Rosa Faner, Judith Garcia-Aymerich, Guillaume Noell, Borja G Cosio, Robert Rodriguez-Roisin, Bartolomé Celli, Josep Maria Anto
The EASI model: A first integrative computational approximation to the natural history of COPD
PloS one
recent evidence suggests alzheimers disease ad genetic risk variants rs1582763 rs6591561 ms4a locus genomewide significant regulators soluble trem2 levels minor allele protective variant rs1582763 associated higher strem2 lower ad risk minor allele rs6591561 relates lower strem2 higher ad risk group previously found higher strem2 relates higher a40 worse bloodbrain barrier bbb integrity measured csfplasma albumin ratio higher csf tau suggesting strong associations amyloid abundance bbb neurodegeneration complicate interpretation expand work leveraging common variants genetic tools tune interpretation high csf strem2 exploring potential modifying role variants wellestablished associations csf strem2 well trem2 transcript levels brain ad neuropathology biomarker analyses leveraged data vanderbilt memory aging project n 127 age 72 643 replicated alzheimers disease neuroimaging initiative n 399 age 73 739 autopsy analyses performed leveraging data religious orders study rush memory aging project n 577 age 89 646 found protective variant rs1582763 attenuated association csf strem2 a40 044 pvalue 0017 replicated interaction adni 027 p 0017 observe interaction effect trem2 mrna levels peptides brain total 014 p 0629 a138 011 p 0200 contrast effects minor allele variant seemed enhance association bloodbrain barrier dysfunction 70e4 p 0009 suggesting elevated strem2 may carry much different interpretation carriers vs noncarriers allele evaluating risk variant rs6591561 across datasets observe statistically significant interaction outcome vmap observed opposing directions associations adni rosmap levels together results suggest protective effect rs1582763 may act decoupling associations strem2 amyloid abundance providing important mechanistic insight strem2 changes highlighting need incorporate genetic context analysis strem2 levels particularly leveraged clinical biomarker disease future