Premium
[P4–413]: MOLECULAR DYNAMIC MODELLING OF A NOVEL PLCG2 VARIANT REVEALS KEY PROTEIN STRUCTURAL DIFFERENCES
Author(s) -
Menzies Georgina E.,
Sims Rebecca,
Williams Julie
Publication year - 2017
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.2017.07.573
Subject(s) - mutation , homology modeling , genetics , amino acid , arginine , molecular dynamics , in silico , biology , protein structure , chemistry , computational biology , gene , biochemistry , enzyme , computational chemistry
Background: Relationships between dementia and eye conditions are poorly understood. Using data from a well-characterized prospective cohort study, we sought to determine whether glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) are associated with increased risk of developing Alzheimer’s disease (AD). Methods: Participants aged 65 and dementia-free were recruited in a prospective, observational cohort. Self-reported smoking history, hypertension, congestive heart failure, diabetes, and history of cardiovascular or cerebrovascular disease were obtained at study visits, and APOEgenotype was obtained from consenting participants. Cognition was evaluated every two years with a screening test. Individuals with low screening test scores had neurological and neuropsychological evaluations. All data were reviewed at consensus conferences to assign participants to diagnostic categories including dementia and probable and possible AD. Eye diagnoses were obtained using ICD-9 codes. Hazard ratios (HR) of developing AD in participants with each of three ophthalmic conditions were compared to those with none of these using Cox regression. Results: A total of 3790 participants were included in the analytic sample. Over 30,627 person-years of follow-up, there were 767 incident cases of AD. In a model controlling for APOEε4 and other covariates, the HR was 1.51 (95%CI 1.13, 2.00) in participants diagnosed with glaucoma 5 years previously, but no increased risk was found among thosewho had glaucoma for > 5 years (HR 0.91, 95%CI 0.74, 1.12). The risks in participants who had AMD for 0-5 years and > 5 years were 1.24 (95%CI 0.99, 1.55) and 1.50 (95%CI 1.24, 1.81). The HR for participants diagnosed with DR for 0-5 years and >5 years were 1.57 (95%CI 0.94, 2.64) and 1.47 (95%CI 1.02, 2.12). Conclusions:Increased risk of ADwas found in participants diagnosed with glaucoma for less than 5 years, and AMD or DR for more than 5 years. Our findings may suggest common pathways between eye diseases and AD. Further studies to determine the potential of eye-based biomarkers of incipient ADmay identify people destined to develop AD.