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Defects in insulin-like growth factor 1 (IGF-1) signaling is a key contributor to Alzheimer's disease (AD). However, the mechanism of how IGF-1 signaling relates to AD remained unclear. Here, we investigated the association of IGF-1 signaling associated biomarkers with AD pathology, sTREM2, and GFAP. Finally, insulin-like growth factor binding protein 2 (IGFBP-2) was associated with AD pathology, and the association was partly medicated by sTREM2 (Aβ42, β= 0.794, p = 0.016; T-tau, β= 0.291, p < 0.001; P-tau181, β= 0.031, p < 0.001) and GFAP (T-tau, β= 0.427, p < 0.001; P-tau181, β= 0.044, p < 0.001). It suggested that sTREM2 and GFAP mediated the relationship between IGF-1 signaling and AD pathology. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) is mainly caused by cerebrovascular injury and may also increase the possibilities of progression to Alzheimer's disease. The present study aims to determine whether plasma neurofilament light (NFL) protein levels could predict the progression of WMH volume in elderly persons without dementia. The present study enrolled 1029 non-dementia participants from the Alzheimer's Disease Neuroimaging Initiative in which all had measurements of plasma NFL and WMH at baseline and 589 had longitudinal measurements during follow-up. Spearman correlation analyses and regression models were used to assess cross-sectional and longitudinal associations between plasma NFL and WMH. Plasma NFL concentration had a moderately strong correlation with WMH at baseline (r = 0.17, p < 0.001). Longitudinal analyses showed that higher baseline plasma NFL concentration was associated with accelerated progression of WMH (β=0.015, p = 0.007). Furthermore, higher change rates of plasma NFL could predict faster progression of WMH in the future (β=0.581, p = 0.002). The results of the study suggest that plasma NFL level might be used as a noninvasive biomarker to track variation trend in WMH in elderly persons without dementia. [ABSTRACT FROM AUTHOR]

Recent findings that human serum contains stably expressed microRNAs (miRNAs) have revealed a great potential of serum miRNA signature as disease fingerprints to diagnosis. Here we used genome-wide serum miRNA expression analysis to investigate the value of serum miRNAs as biomarkers for the diagnosis of Alzheimer's disease (AD). Illumina HiSeq 2000 sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 50 AD patients and 50 controls in the screening stages. The detected serum miRNAs then were validated by qRT-PCR in 158 patients and 155 controls. MiR-98-5p, miR-885-5p, miR-483-3p, miR-342-3p, miR-191-5p, and miR-let-7d-5p displayed significantly different expression levels in AD patients compared with controls. Among the 6 miRNAs, miR-342-3p has the best sensitivity (81.5%) and specificity (70.1%) and was correlated to Mini-Mental State Examination score. This study identified six serum miRNAs that distinguish AD patients from healthy controls with high sensitivity and specificity. Serum miRNA panel (or miR-342-3p alone) may serve as a novel, noninvasive biomarker for AD. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence supports an important role of vascular risk in cognitive decline and dementia.Objective: This study aimed to examine whether vascular risk was associated with cognitive decline, cerebral hypometabolism, and clinical progression in cognitively intact elders.Methods: Vascular risk was assessed by the Framingham Heart Study general Cardiovascular disease (FHS-CVD) risk score. The cross-sectional and longitudinal associations of FHS-CVD risk score with cognition and brain glucose metabolism were explored using multivariate linear regression and linear mixed effects models, respectively. The risk of clinical progression conversion was assessed using Kaplan-Meier survival curves and multivariate Cox proportional hazard models.Results: A total of 491 cognitively intact elders were included from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants with high FHS-CVD risk scores had lower baseline Mini-Mental State Examination (MMSE) (p = 0.009), executive function (EF) (p < 0.001), memory function (MEM) (p < 0.001) scores, and F18-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake (p < 0.001) than those with low FHS-CVD risk scores. In longitudinal analyses, individuals with higher FHS-CVD risk scores had greater longitudinal declines in MMSE (p = 0.043), EF (p = 0.029) scores, and FDG-PET uptake (p = 0.035). Besides, individuals with a higher vascular risk had an increased risk of clinical progression (p = 0.004).Conclusion: These findings indicated effects of vascular risk on cognitive decline, cerebral hypometabolism, and clinical progression. Early detection and management of vascular risk factors might be useful in the prevention of dementia. [ABSTRACT FROM AUTHOR]

Background: The role of cerebral microbleeds (CMBs) in cognitive impairment remains controversial.Objective: To investigate the possible links between the presence, progression, number, and location of CMBs and cognition.Methods: We assessed 792 subjects from the Alzheimer's Disease Neuroimaging Initiative who underwent both brain 3 Tesla MRI scans and cognitive testing. The association between CMBs and cognitive change was explored using linear mixed-effects models (LME).Results: Presence and number of CMBs were associated with memory (β= -0.03, p = 0.015; β= -0.01, p = 0.003), executive function (β= -0.04, p = 0.010; β= -0.01, p = 0.014), and global cognitive function (β= -0.06, p = 0.025; β= -0.03, p < 0.001). Progression of CMBs showed significant negative associations with executive function (β= -0.05, p = 0.025) and global cognitive function (β= -0.12, p = 0.015). The relations with cognitive performance (memory, executive function and global cognitive function) were mainly driven by lobar CMBs (β= -0.03, p = 0.041; β= -0.04, p = 0.010; β= -0.07, p = 0.029, respectively), especially those located in temporal lobe (β= -0.08, p = 0.027; β= -0.13, p = 0.001; β= -0.26, p < 0.001, respectively). Furthermore, white matter hyperintensities may mediate the association between CMBs and cognition.Conclusion: The presence, progression, number, and location of CMBs, especially those located in temporal lobe, are associated with cognitive decline. These findings suggest CMBs play a role in cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Bridging integrator 1 (BIN1) has been identified as one of the most associated loci for Alzheimer's disease (AD), and recently was reported to modulate tau pathology to mediate AD in vitro. However, the effects of BIN1 on the AD related biomarkers in AD continuum were not specifically assessed. Objective: We explored the effects of BIN1 loci on AD specific biomarkers (CSF proteins, brain structures, glucose and amyloid-β (Aβ) metabolisms) to investigate the role BIN1 in AD pathogenesis. Methods: We calculated the associations of BIN1 loci with these markers at baseline and follow-up in multiple linear models in 812 ADNI subjects. Results: BIN1 loci were significantly associated with the levels of T-tau (rs744373: pc = 0.047, rs13031703: pc = 0.042) and P-tau (rs744373: pc = 0.044, rs13031703: pc = 0.019), but not with Aβ in CSF test. BIN1 genotypes were strongly related to atrophy of hippocampus (rs7561528: pc = 0.011), CA1 (rs1469980: pc = 0.029) and parahippocampus (rs72838284, pc = 0.017) on MRI, and to glucose metabolism on FDG-PET, but not to Aβ deposition on AV45-PET imaging. Furthermore, haplotype and subgroup analysis confirmed these significant findings. In addition, the loci associated with these markers were also identified to influence the risk for AD in the meta-analysis of 74 046 European individuals. Conclusion: This study supported that BIN1 contributes to the risk of AD by altering neural degeneration (abnormal tau, brain atrophy and glucose metabolism) but not Aβ pathology. [ABSTRACT FROM AUTHOR]

Background: Vascular dementia (VaD) is the second most common type of dementia. So far, little is known about the contribution of genetic polymorphisms to the risk of VaD. Many candidate genetic polymorphisms have been examined in a large number of studies. However, due to the conflicting results, the genetics of VaD is still behind the shadow.Objective: We conducted a comprehensive meta-analysis on associations between genetic polymorphisms of any gene and VaD to investigate the genetics of VaD.Method: We sought the published studies of associations between any genetic polymorphism and VaD and critically appraised them. We assessed the effects of genetic models by calculating pooled odds ratios (ORs), investigating the origin of heterogeneity by subgroup analysis, and testing the robustness by random effect model and sensitivity analysis.Results: 69 studies with 4,462 cases and 11,583 controls were included. We identified APOE ɛ2/ɛ3/ɛ4 and additional four genetic polymorphisms including MTHFR C677T, PON1 L55M, TGF-β1 +29C/T, and TNF-α -850C/T associated with VaD. Tested by random effect model and sensitivity analysis, the pooled results show nice robustness.Conclusions: Our comprehensive meta-analysis highlighted the genetic contribution to sporadic VaD. Because of the small amount of data on associations between genetic polymorphisms, except for APOE, and VaD, more studies are needed to test the existing genetic polymorphisms and detect other related genetic variants. [ABSTRACT FROM AUTHOR]

TREM2 has been reported to be associated with Alzheimer's disease (AD). Here, we evaluated TREM2 mRNA and protein expressions in peripheral blood from AD patients and healthy controls. Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients. We observed a significant correlation between TREM2 expressions and MMSE score (mRNA: r = -0.482, protein: r = -0.582; p < 0.01). According to ROC curve analysis, the diagnostic accuracy for TREM2 protein levels on monocytes was 70%, with the sensitivity and specificity 68% and 72%, respectively. Our results indicate that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis. [ABSTRACT FROM AUTHOR]