AUTHOR=Song Ya-Nan , Li Jie-Qiong , Tan Chen-Chen , Wang Hui-Fu , Tan Meng-Shan , Cao Xi-Peng , Yu Jin-Tai , Tan Lan ,  the Alzheimer’s Disease Neuroimaging Initiative 

TITLE=TREML2 Mutation Mediate Alzheimer’s Disease Risk by Altering Neuronal Degeneration

JOURNAL=Frontiers in Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.00455

DOI=10.3389/fnins.2019.00455

ISSN=1662-453X

ABSTRACT=<p>A coding missense mutation (rs3747742) in triggering receptor expressed on myeloid cell-like 2 (<italic>TREML2</italic>) has been recently proposed as an important protective factor against Alzheimer’s disease (AD). However, the link between <italic>TREML2</italic> and AD pathology remains unclear. Therefore, we explored the association of <italic>TREML2</italic> 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-β (Aβ<sub>1-42</sub>). 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 <italic>TREML2</italic> rs3747742 with the baseline variables. Furthermore, we also calculated the change rate of above variables influenced by <italic>TREML2</italic> 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, <italic>TREML2</italic> rs3747742 exhibited a strong association with CSF total-tau levels at baseline (β = -22.1210, <italic>p</italic> = 0.0166) and 4-year follow-up (β = -0.3961, <italic>p</italic> = 0.0115). Furthermore, no associations were found with CSF Aβ<sub>1-42</sub> levels, P-tau levels, neuroimaging biomarkers and cognitive function neither for baseline variables nor for longitudinal data. Thus, this study indicated that <italic>TREML2</italic> mediated the risk of AD through influencing AD-related neurodegeneration (abnormal T-tau levels) but not P-tau levels and Aβ pathology.</p>