Journal
FRONTIERS IN NEUROSCIENCE
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2019.00455
Keywords
TREML2; neurodegeneration; Alzheimer's disease; CSF biomarkers; Alzheimer's disease neuroimaging initiative
Categories
Funding
- National Key R&D Program of China [2016YFC1305803]
- Shandong Provincial Outstanding Medical Academic Professional Program
- Taishan Scholars Program of Shandong Province [ts201511109, tsqn20161078, tsqn20161079]
- Qingdao Key Health Discipline Development Fund
- Qingdao Outstanding Health Professional Development Fund
- Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders
- Research Award Fund for Outstanding Young and Middle-aged Scientists of Shandong Province [BS2015SW006]
- Projects of medical and health technology development program in Shandong Province [2015WSA02054]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd.
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
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A coding missense mutation (rs3747742) in triggering receptor expressed on myeloid cell-like 2 (TREML2) has been recently proposed as an important protective factor against Alzheimer's disease (AD). However, the link between TREML2 and AD pathology remains unclear. Therefore, we explored the association of TREML2 rs3747742 with cognitive function, neuroimaging biomarkers and cerebrospinal fluid (CSF) biomarkers related to AD, including CSF total-tau (T-tau), phosphor-tau (P-tau), and amyloid-beta (A beta(1-)(42)). As for cognitive function, related cognitive scores of Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer's Disease Assessment Scale-cognitive section 11 (ADAS-cog 11), Mini-Mental State Examination (MMSE), and Rey Auditory-Verbal Learning Test (RAVLT) were extracted. We used a multiple linear regression model to examine the association of TREML2 rs3747742 with the baseline variables. Furthermore, we also calculated the change rate of above variables influenced by TREML2 rs3747742 via applying a mixed-effects model over a 4-year follow-up. In this analysis, a total of 1,306 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Finally, we observed that only in AD patients, but not in normal controls or mild cognitive impairment (MCI) individuals, TREML2 rs3747742 exhibited a strong association with CSF total-tau levels at baseline (beta = -22.1210, p = 0.0166) and 4-year follow-up (beta = -0.3961, p = 0.0115). Furthermore, no associations were found with CSF A beta(1)(-42) levels, P-tau levels, neuroimaging biomarkers and cognitive function neither for baseline variables nor for longitudinal data. Thus, this study indicated that TREML2 mediated the risk of AD through influencing AD-related neurodegeneration (abnormal T-tau levels) but not P-tau levels and A beta pathology.
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