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As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A −) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p < 0.001) in PSQI were positively associated with CSF sTREM2. Besides, several U-shaped relationships were revealed of sleep-time measures, such as insufficient or excessive nocturnal sleep duration, with CSF sTREM2 in A + individuals (the optimal model: bedtime 22:21 p.m., time to fall asleep 22:52 p.m., nocturnal sleep duration 7.36 h). In A − individuals, the above relationships were not found. Poor self-reported sleep characteristics and sleep indicators were associated with higher CSF sTREM2, suggesting that sleep might play an important role in the regulation of TREM2-associated microglial activity. [ABSTRACT FROM AUTHOR]

Relationship between serum calcium and Alzheimer's disease (AD) remains unclear. The aim of this study is to test whether serum calcium is associated with other AD-associated biomarkers and could predict clinical progression in nondemented elders. This was a longitudinal population-based study. The sample was derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, which included 1224 nondemented elders: 413 cognitively normal (CN) and 811 mild cognition impairment (MCI). Associations were investigated between serum calcium and longitudinal changes in Aβ/tau pathologic features, brain structure, cognitive function, and disease progression. Serum calcium concentrations increased with disease severity. Serum calcium predicted longitudinal cognitive decline and conversion from nondemented status to AD dementia (adjusted HR = 1.41, 95% CI 1.13–1.76). Furthermore, serum calcium levels were negatively correlated with CSF-Aβ42 (β = − 0.558, P = 0.008), FDG-PET (β = − 0.292, P < 0.001), whole brain volume (β = − 0.148, P = 0.001), and middle temporal volume (β = − 0.216, P = 0.042). Similar results were obtained in CN and MCI groups. Higher serum calcium status (even if not hypercalcemia) may increase the risk of AD in elders. Serum calcium is a useful biomarker in predicting clinical progression in nondemented elders. More researches are needed in the future to explore the underlying mechanism. [ABSTRACT FROM AUTHOR]

Triggering receptor expressed on myeloid cells-1 (TREM1) has been reported to associate with Alzheimer's disease (AD) pathology. Recently, TREM1 variant rs2234246A was reported to regulate TREM-1 protein and mRNA levels. We explored the effect of rs2234246 on AD specific biomarker (amyloid-β PET) to look into the role of this TREM1 locus in AD pathogenesis. We calculated the association of the TREM1 locus with amyloid deposition at baseline and follow-up using both multiple linear models and mixed effect models respectively in 522 the Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. We also analyzed the association of TREM1 with this marker in subregions during the AD process. In the pooled sample, TREM1 rs2234246A was associated with the levels of mean standard uptake volume ratios (SUVRs) at baseline (p = 0.02) and the length of follow-up (p = 0.04) in the cross-sectional analysis and longitudinal study. Subgroup analyses showed no correlation between rs2234246A and amyloid deposition in the cognitively normal (CN) group. In the mild cognitive impairment (MCI) group, TREM1 rs2234246A reached significance at baseline (p = 0.04) and the length of follow-up (p = 0.04). In the AD group, TREM1 rs2234246A was associated with mean SUVR at baseline (p < 0.001) and the length of follow-up (p = 0.001). In subregion analyses, TREM1 rs2234246A was detected to be related to Aβ deposition. This study demonstrated an association between TREM1 variant rs2234246 and brain amyloidosis. Our findings implied that this variant is involved in AD by influencing Aβ neuropathology. [ABSTRACT FROM AUTHOR]

Correlation between the level of high-sensitivity C-reactive protein (hs-CRP) and the incidence of intracranial arterial stenosis (ICAS) is unclear. We aim to investigate the relationship between hs-CRP levels and ICAS. A total of 1458 patients aged ≥ 40 years were enrolled in this study. All the participants had a magnetic resonance angiography (MRA) examination for the evaluation of ICAS. Participants were classified into four groups according to stroke and ICAS. Multivariable logistic regression models were used to assess the relationship of hs-CRP levels and ICAS status. A total of 432 (29.63%) subjects had ICAS. The levels of hs-CRP in stroke group were significantly higher than those in non-stroke group (p < 0.001). Patients with ICAS tend to have higher hs-CRP levels (p < 0.001). In multivariate analysis, the fourth hs-CRP quartile had the strongest association with ICAS in both stroke group and non-stroke group (OR 2.512, 95% CI 1.651–3.853, p < 0.001 for stroke group, and OR 2.534, 95% CI 1.435–4.595, p = 0.002 for non-stroke group) among the four quartiles of hs-CRP levels. Our study suggests that elevated serum hs-CRP levels are associated with higher risk of ICAS, in both stroke patients and non-stroke participants. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds are the presence of a group of pathological processes affecting the small arteries, arterioles, capillaries, and venules of the brain. Previous studies showed that cerebral microbleeds were associated with higher risk of dementia and stroke. We conducted a genome-wide association study of cerebral microbleeds to identify novel loci associated with the presence and progression of cerebral microbleeds. This study included 454 individuals composed by 176 subjects with cerebral microbleeds and 278 subjects without cerebral microbleeds in a non-Hispanic/Latino white population. Association of genetic variants with the presence and progression of cerebral microbleeds was assessed by logistic regression model. Potential genetic risk variants Apolipoprotein E (ApoE) polymorphisms were independently genotyped and checked the association with the presence and progression of cerebral microbleeds. No single-nucleotide polymorphisms (SNPs) associated with the presence or progression of cerebral microbleeds were identified at genome-wide significant level (P < 1 × 10−8). A total of 19 SNPs were associated with the presence of microbleeds at suggestive level (P < 1 × 10−5). One SNP was associated with lower progression risk for cerebral microbleeds with suggestive evidence (P < 1 × 10−5). ApoE ε4ε4 was independently associated with the presence and progression of cerebral microbleeds (odds ratio = 2.54, 95% confidence interval 1.08–6.00 and odds ratio = 5.1, 95% confidence interval 1.36–19.16). We highlighted 19 novel SNPs associated with the presence of cerebral microbleeds and one novel SNP associated with the progression of cerebral microbleeds for the first time. ApoE ε4ε4 was confirmed independently associated with the presence and progression of cerebral microbleeds. [ABSTRACT FROM AUTHOR]

α-Synuclein is a 140-amino acid protein produced predominantly by neurons in the brain which plays a role in the regulation of neurotransmitter release, synaptic function, and plasticity, thus making it the focus in understanding the etiology of a group of neurodegenerative diseases. We conducted genome-wide association studies (GWAS) of α-synuclein levels in cerebrospinal fluid (CSF) with 209 non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort using a linear regression model to identify novel variants associated with α-synuclein concentration. The minor allele (T) of rs7072338 in the long intergenic non-protein coding RNA 1515 (LINC01515) and the minor allele (T) of rs17794023 in clusterin-associated protein 1 (CLUAP1) were associated with higher CSF α-synuclein levels at genome-wide significance (P = 4.167 × 10-9 and 9.56 × 10-9, respectively). In addition, single nucleotide polymorphisms (SNPs) near amyloid beta precursor protein (APP) (rs1394839) (P = 2.31 × 10-7), Rap guanine nucleotide exchange factor 1 (RAPGEF1) (rs10901091) (P = 8.07 × 10-7), and two intergenic loci on chromosome 2 and 14 (rs11687064 P = 2.50 × 10-7and rs7147386 P = 4.05 × 10-7) were identified as suggestive loci associated with CSF α-synuclein levels. We have identified significantly associated SNPs for CSF α-synuclein. These associations have important implications for a better understanding of α-synuclein regulation and allow researchers to further explore the relationships between these SNPs and α-synuclein-related neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder. At present, there are no effective disease-modifying therapies, and the cause of the disease remains unclear. Previously, almost all researchers focus on the brain for exploring the pathogenesis and therapeutic strategies in AD. A recent study by Xiang et al. (Acta Neuropathol 130:487-499, ) reported the significance of the physiological capacity of peripheral tissues and organs in clearing brain-derived amyloid-beta (Aβ), which opens a novel avenue to understand the AD pathogenesis and develop therapies for AD. [ABSTRACT FROM AUTHOR]