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Background: rs9357347 located at the triggering receptor expressed on myeloid cells (TREM) gene cluster could increase TREM2 and TREM-like transcript 1 (TREML1) brain gene expression, which is considered to play a protective role against Alzheimer's disease (AD). Objectives: To investigate the role of rs9357347 in AD pathogenesis by exploring the effects of rs9357347 on AD specific biomarkers. Methods: This study analyzed the association of rs9357347 with AD-related cerebrospinal fluid (CSF) and neuroimaging markers from 201 cognitively normal (CN) older adults, 349 elders with mild cognitive impairment (MCI), and 172 elders with AD dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We next analyzed the association in 259 amyloid-β positive (Aβ+) elders and 117 amyloid-β negative (Aβ-) elders (Aβ+: CSF Aβ1-42 ≤ 192 pg/ml; Aβ-: CSF Aβ1-42 > 192 pg/ml). Associations were tested using multiple linear regression models at baseline. Furthermore, multiple mixed-effects models were used in a longitudinal study which lasted 4 years. Results: At baseline, we found that rs9357347 had association with CSF Aβ1-42 in CN group (β = 0.357, P = 0.009). In AD group, rs9357347 was associated with total tau (T-tau) level (β = -0.436, P = 0.007). Moreover, the strong influence exerted by rs9357347 on T-tau was also seen in Aβ+ group (β = -0.202, P = 0.036). In the longitudinal study, rs9357347 was also found to be associated with Aβ1-42 in CN group (β = 0.329, P = 0.023). In AD group, the mutation of rs9357347 was associated with slower accumulation of T-tau (β = -0.472, P = 0.002) and tau phosphorylated at threonine 181 [P-tau 181 (β = -0.330, P = 0.019)]. Furthermore, the obvious influence exerted by rs9357347 on T-tau was also seen in Aβ+ group (β = -0.241, P = 0.013). Conclusion: This study suggested that rs9357347 reduced the risk of AD by modulating both amyloid-β pathology and neuronal degeneration.
Pubmed ID: 31379492
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Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsBiomedical technology resource center specializing in novel approaches and tools for neuroimaging. It develops novel strategies to investigate brain structure and function in their full multidimensional complexity. There is a rapidly growing need for brain models comprehensive enough to represent brain structure and function as they change across time in large populations, in different disease states, across imaging modalities, across age and sex, and even across species. International networks of collaborators are provided with a diverse array of tools to create, analyze, visualize, and interact with models of the brain. A major focus of these collaborations is to develop four-dimensional brain models that track and analyze complex patterns of dynamically changing brain structure in development and disease, expanding investigations of brain structure-function relations to four dimensions.
View all literature mentionsDatabase of the results of the ADNI study. ADNI is an initiative to develop biomarker-based methods to detect and track the progression of Alzheimer's disease (AD) that provides access to qualified scientists to their database of imaging, clinical, genomic, and biomarker data.
View all literature mentionsA public charity whose mission is to support the NIH in its mission to improve health, by forming and facilitating public-private partnerships for biomedical research and training. Its vision is Building Partnerships for Discovery and Innovation to Improve Health. The FNIH draws together the world''s foremost researchers and resources, pressing the frontier to advance critical discoveries. They are recognized as the number-one medical research charity in the countryleveraging support, and convening high level partnerships, for the greatest impact on the most urgent medical challenges we face today. Grants are awarded as part of a public-private partnership with the National Heart, Lung, and Blood Institute (NHLBI) on behalf of The Heart Truth in support of women''s heart health education and research. Funding for the Community Action Program is provided by the FNIH through donations from individuals and corporations including The Heart Truth partners Belk Department Stores, Diet Coke, and Swarovski. Successful biomedical research relies upon the knowledge, training and dedication of those who conduct it. Bringing multiple disciplines to bear on health challenges requires innovation and collaboration on the part of scientists. Foundation for NIH partnerships operate in a variety of ways and formats to recruit, train, empower and retain their next generation of researchers. From lectures and multi-week courses, to scholarships and awards through fellowships and residential training programs, their programs respond to the needs of scientists at every level and stage in their careers.
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