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A Candidate Regulatory Variant at the TREM Gene Cluster Confer Alzheimer's Disease Risk by Modulating Both Amyloid-? Pathology and Neuronal Degeneration.

ABSTRACT: 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-? positive (A?+) elders and 117 amyloid-? negative (A?-) elders (A?+: CSF A?1-42 ? 192 pg/ml; A?-: CSF A?1-42 > 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 A?1-42 in CN group (? = 0.357, P = 0.009). In AD group, rs9357347 was associated with total tau (T-tau) level (? = -0.436, P = 0.007). Moreover, the strong influence exerted by rs9357347 on T-tau was also seen in A?+ group (? = -0.202, P = 0.036). In the longitudinal study, rs9357347 was also found to be associated with A?1-42 in CN group (? = 0.329, P = 0.023). In AD group, the mutation of rs9357347 was associated with slower accumulation of T-tau (? = -0.472, P = 0.002) and tau phosphorylated at threonine 181 [P-tau 181 (? = -0.330, P = 0.019)]. Furthermore, the obvious influence exerted by rs9357347 on T-tau was also seen in A?+ group (? = -0.241, P = 0.013). Conclusion: This study suggested that rs9357347 reduced the risk of AD by modulating both amyloid-? pathology and neuronal degeneration.

SUBMITTER: Tian ML

PROVIDER: S-EPMC6650562 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Candidate Regulatory Variant at the TREM Gene Cluster Confer Alzheimer's Disease Risk by Modulating Both Amyloid-β Pathology and Neuronal Degeneration.

Tian Mei-Ling ML Ni Xiao-Neng XN Li Jie-Qiong JQ Tan Chen-Chen CC Cao Xi-Peng XP Tan Lan L

Frontiers in neuroscience 20190717

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 c ...[more]

PMID: 31379492

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Dataset Information

A Candidate Regulatory Variant at the TREM Gene Cluster Confer Alzheimer's Disease Risk by Modulating Both Amyloid-? Pathology and Neuronal Degeneration.

Publications

A Candidate Regulatory Variant at the <i>TREM</i> Gene Cluster Confer Alzheimer's Disease Risk by Modulating Both Amyloid-β Pathology and Neuronal Degeneration.

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