Relationship Between Peripheral Transport Proteins and Plasma Amyloid-β in Patients with Alzheimer’s Disease Were Different from Cognitively Normal Controls: A Propensity Score Matching Analysis

2020 ◽  
Vol 78 (2) ◽  
pp. 699-709
Author(s):  
Ling Gao ◽  
Jin Wang ◽  
Yu Jiang ◽  
Shan Wei ◽  
Suhang Shang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Amyloid Β ◽  
Transport Proteins ◽  
Cognitively Normal ◽  
Propensity Score Matching Analysis ◽  
Soluble Rage ◽  
Peripheral Clearance

Background: Transport proteins, soluble LRP1 (sLRP1) and soluble RAGE (sRAGE), play a pivotal role in the peripheral clearance of plasma amyloid-β (Aβ). However, their relationship is seldom discussed, especially in Alzheimer’s disease (AD). Objective: To explore whether their relationship in patients with AD varied from those in cognitively normal (CN) controls. Methods: We initially recruited 70 patients with AD and 725 CN controls, then applied propensity score matching (PSM) analysis to balance the differences between two groups. Plasma levels of sLRP1, sRAGE, and Aβ were measured using commercial ELISA kits and log transformed when skewed distributed. The relationship between sLRP1/sRAGE and plasma Aβ were analyzed using Pearson’s correlation analysis followed by multiple linear regression separately in the original population and matched participants. Results: After PSM, 70 patients with AD and 140 matched controls were included for further analysis. Log sLRP1 was positively correlated with plasma Aβ40 in matched CN controls (r = 0.222, p = 0.008) but not in patients with AD (r = 0.137, p = 0.260). After multivariable adjustment, Log sLRP1 remained significantly associated with plasma Aβ40 in the CN group (β= 7.347, p = 0.014) but not in the AD group (β= 10.409, p = 0.105). In contrast, Log sLRP1 was not correlated with plasma Aβ42 in patients with AD or CN controls, and Log sRAGE was consistently not associated with plasma Aβ40 or Aβ42 in either group. Conclusion: The significant correlation between sLRP1 and plasma Aβ40 present in CN controls was not found in patients with AD, suggesting that their relationship was different in AD. However, the specific mechanisms and its influence on cerebral amyloid burden require further validation.

scholarly journals Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Jonathan D. Drake ◽  
Alison B. Chambers ◽  
Brian R. Ott ◽  
Lori A. Daiello ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Intercellular Adhesion Molecule ◽  
Csf Biomarkers ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer’s disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. Objective: We utilized Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. Methods: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). Results: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-β (Aβ 42), total tau, phosphorylated tau (P-tau), or P-tau/Aβ 42 (all <  p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. Conclusion: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.

Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

Monocytes in the Peripheral Clearance of Amyloid-β and Alzheimer’s Disease

2019 ◽  
Vol 68 (4) ◽  
pp. 1391-1400 ◽  
Author(s):  
Huifang Guo ◽  
Zhaohua Zhao ◽  
Ruisan Zhang ◽  
Peng Chen ◽  
Xiaohua Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Peripheral Clearance

scholarly journals Amyloid-beta uptake by blood monocytes is reduced with ageing and Alzheimer’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Si-Han Chen ◽  
Ding-Yuan Tian ◽  
Ying-Ying Shen ◽  
Yuan Cheng ◽  
Dong-Yu Fan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Blood Levels ◽  
Amyloid Β Protein ◽  
Blood Monocytes ◽  
Cognitively Normal ◽  
Β Protein ◽  
Toll Like Receptor 2 ◽  
Age And Sex

AbstractDeficits in the clearance of amyloid β-protein (Aβ) play a pivotal role in the pathogenesis of sporadic Alzheimer’s disease (AD). The roles of blood monocytes in the development of AD remain unclear. In this study, we sought to investigate the alterations in the Aβ phagocytosis function of peripheral monocytes during ageing and in AD patients. A total of 104 cognitively normal participants aged 22–89 years, 24 AD patients, 25 age- and sex-matched cognitively normal (CN) subjects, 15 Parkinson’s disease patients (PD), and 15 age- and sex-matched CN subjects were recruited. The Aβ uptake by blood monocytes was measured and its alteration during ageing and in AD patients were investigated. Aβ1-42 uptake by monocytes decreased during ageing and further decreased in AD but not in PD patients. Aβ1-42 uptake by monocytes was associated with Aβ1-42 levels in the blood. Among the Aβ uptake-related receptors and enzymes, the expression of Toll-like receptor 2 (TLR2) was reduced in monocytes from AD patients. Our findings suggest that monocytes regulate the blood levels of Aβ and might be involved in the development of AD. The recovery of the Aβ uptake function by blood monocytes represents a potential therapeutic strategy for AD.

scholarly journals Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

2019 ◽  
Vol 15 (6) ◽  
pp. 764-775 ◽  
Author(s):  
Andrea Vergallo ◽  
Lucile Mégret ◽  
Simone Lista ◽  
Enrica Cavedo ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Amyloid Β ◽  
Cognitively Normal ◽  
Cerebral Amyloidosis ◽  
Normal Individuals

Cortisol, Amyloid-β, and Reserve Predicts Alzheimer’s Disease Progression for Cognitively Normal Older Adults

2019 ◽  
Vol 70 (2) ◽  
pp. 553-562 ◽  
Author(s):  
Chinedu T. Udeh-Momoh ◽  
Bowen Su ◽  
Stephanie Evans ◽  
Bang Zheng ◽  
Shireen Sindi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Amyloid Β ◽  
Cognitively Normal

scholarly journals Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease

2019 ◽  
Vol 11 (507) ◽  
pp. eaav6221 ◽  
Author(s):  
Michael Ewers ◽  
Nicolai Franzmeier ◽  
Marc Suárez-Calvet ◽  
Estrella Morenas-Rodriguez ◽  
Miguel Angel Araque Caballero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Elderly Subjects ◽  
Amyloid Β Peptide ◽  
Loss Of Function ◽  
Clinical Progression ◽  
Cognitively Normal ◽  
Soluble Trem2

Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF Aβ1–42 (amyloid β-peptide 1 to 42; A+) and CSF p-tau181 (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF Aβ1–42 and CSF p-tau181 (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau181 concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF Aβ1–42 and CSF p-tau181. These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.

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