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P2‐148: ALZHEIMER'S‐RELATED CEREBROVASCULAR DISEASE IN DOWN SYNDROME
Author(s) -
Lao Patrick J.,
Gutierrez Jose,
Lai Florence,
Rosas H. Diana,
Keator David,
Igwe Kay C.,
Banerjee Arit,
Laing Krystal K.,
Hsu Eugene,
Sathishkumar Mithra,
Yassa Michael A.,
Silverman Wayne,
Lott Ira T.,
Schupf Nicole,
Brickman Adam M.
Publication year - 2019
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 - 10.1016/j.jalz.2019.06.2555
Subject(s) - dementia , medicine , hyperintensity , disease , vascular dementia , biomarker , cardiology , pathology , alzheimer's disease , population , magnetic resonance imaging , radiology , biochemistry , chemistry , environmental health
through the development of more sophisticated methods for SNP selection and weight allocation. Enhanced performance is also attributable to study design factors and disease characteristics (Figure 2). Examples include controlling for population stratification, increasing sample size, adequate training/testing splitting ratio among others. Applications of PRS include risk stratification, clinical trial sample enrichment, AD-subtype determination, association to disease stage and rate of progression, and prediction of age at onset (AAO). AAO of AD in particular is modulated by PRS which can accelerate AAO from 8 months to 10 years. Studies to date highlight the diversity of the AD mechanisms and the stage-specific manifestation of the genetic influence. Evidence of association of PRS with quantitative endophenotypes such as MRI, PET and CSF has been limited by sample availability and sizes and SNP inclusion threshold choices. Conclusions: Although not ready for clinical application yet, increased sample sizes are expected to improve risk prediction accuracy. Integration of endophenotype measurements in PRS calculation may be a key for its application in precision medicine. Finally, improvement of PRS’s interpretability may enhance the understanding of AD pathogenesis and lead to novel therapeutic development.