scholarly journals Assessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer’s Disease

2021 ◽  
pp. 1-14
Author(s):  
Alex Handy ◽  
Jodie Lord ◽  
Rebecca Green ◽  
Jin Xu ◽  
Dag Aarsland ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Plasma ◽  
Plasma Proteins ◽  
Statistical Power ◽  
Binding Protein ◽  
Risk Scores ◽  
Causal Pathway ◽  
Genetic Overlap ◽  
Blood Plasma Proteins

Background: Blood plasma proteins have been associated with Alzheimer’s disease (AD), but understanding which proteins are on the causal pathway remains challenging. Objective: Investigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR). Methods: Following a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/–PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR. Results: For APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p <  0.00017). No protein APOE- PRS or AD PRS (APOE+/–) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p = 0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p = 0.025, protein APOE- PRS p = 0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the five proteins demonstrated a causal association (p <  0.05) in either direction. Conclusion: Apolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, accessible risk factor. While evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.

scholarly journals Assessing genetic overlap and causality between blood plasma proteins and Alzheimer’s Disease

2021 ◽  
Author(s):  
Alex Handy ◽  
Jodie Lord ◽  
Rebecca Green ◽  
Jin Xu ◽  
Dag Aarsland ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Plasma ◽  
Plasma Proteins ◽  
Binding Protein ◽  
Risk Scores ◽  
P Value ◽  
Causal Pathway ◽  
Genetic Overlap ◽  
Blood Plasma Proteins

ABSTRACTBackground Blood plasma proteins are modifiable and have been associated with Alzheimer’s disease (AD), but understanding which proteins are on the causal pathway remains challenging.ObjectiveInvestigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian Randomization (MR).MethodsFollowing a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritised proteins with and without the apolipoprotein E region (APOE+/- PRS) and tested for association with AD status across three cohorts (n=6244). An AD PRS was also tested for association with protein levels in one cohort (n=410). Proteins showing association with AD were taken forward for MR.ResultsFor APOE e3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p-value <0.00017). No protein APOE-PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p-value=0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p-value=0.025, protein APOE-PRS p-value=0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the 5 proteins demonstrated a causal association (p-value<0.05) in either direction.ConclusionApolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, modifiable risk factor. Whilst evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.

scholarly journals Early Detection of Alzheimer's Disease with Blood Plasma Proteins Using Support Vector Machines

2021 ◽  
Vol 25 (1) ◽  
pp. 218-226
Author(s):  
Chima S. Eke ◽  
Emmanuel Jammeh ◽  
Xinzhong Li ◽  
Camille Carroll ◽  
Stephen Pearson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Support Vector Machines ◽  
Early Detection ◽  
Blood Plasma ◽  
Plasma Proteins ◽  
Support Vector ◽  
Vector Machines ◽  
Blood Plasma Proteins

The level of carbonylation of plasma proteins and peripheral blood leukocytes in patients with different duration of Alzheimer’s disease

2021 ◽  
pp. 235-243
Author(s):  
Petrov Dmitriy Sergeevich Petrov Dmitriy Sergeevich ◽  
Mariya Germanovna Engalycheva ◽  
Natalya Vasilievna Korotkova ◽  
Ulugbek Usmanovich Ochilov
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Plasma ◽  
Peripheral Blood ◽  
Plasma Proteins ◽  
Oxidative Modification ◽  
Mononuclear Leukocytes ◽  
Adaptive Potential ◽  
Oxidative Modification Of Proteins

The course of Alzheimer’s disease is associated with an increase in oxidative stress associated with an increase in the production of reactive oxygen species against the background of neurodegenerative inflammation, and a simultaneous depletion of the antioxidant defense capabilities of brain cells. The result is the oxidative modification of macromolecules: proteins, lipids, nucleic acids. Protein carbonylation products accumulate not only in neurons, and in direct correlation with the degree of increase in amyloidosis and neurodegeneration, but also in extra-neuronal tissues, including leukocytes. In the course of this study, the levels of spontaneous and induced oxidative modification of proteins were determined in the blood plasma and fractionated leukocytes of peripheral blood of patients with different durations of Alzheimer’s disease, and the value of the reserve-adaptive potential was assessed as markers of the severity of oxidative stress. It has been established that the course of Alzheimer’s disease has a greater effect on the accumulation of carbonyl derivatives in blood plasma. In patients with a disease duration of 5–10 years, the total level of aldehyde and ketone derivatives of modified plasma proteins exceeds the same indicator in subgroups with a shorter duration of the disease. This tendency is less typical for mononuclear leukocytes. The level of induced oxidative modification of proteins increases to a greater extent in blood plasma than in fractionated leukocytes. This indicates the depletion of the reserve-adaptive potential of plasma antioxidant capabilities, which is more pronounced in patients with a long course of Alzheimer’s disease. For polymorphonuclear leukocytes, such a pattern was not revealed, which is probably associated with a short cell life. In mononuclear leukocytes, as well as in plasma, there is a tendency to depletion of the reserve-adaptive potential, but to a lesser extent.

Post-Translational Oxidation Modifications of Blood Plasma Proteins of Cosmonauts after a Long-term Flight: Part I

2020 ◽  
Vol 46 (5) ◽  
pp. 531-539
Author(s):  
I. M. Larina ◽  
A. G. Brzhzovsky ◽  
A. M. Nosovsky ◽  
A. S. Kononikhin ◽  
O. I. Orlov
Keyword(s):  
Blood Plasma ◽  
Plasma Proteins ◽  
Blood Plasma Proteins

scholarly journals BIOPHYSICAL STUDIES OF BLOOD PLASMA PROTEINS

1946 ◽  
Vol 165 (1) ◽  
pp. 21-35 ◽  
Author(s):  
H.F. Deutsch ◽  
R.A. Alberty ◽  
L.J. Gosting
Keyword(s):  
Blood Plasma ◽  
Plasma Proteins ◽  
Biophysical Studies ◽  
Blood Plasma Proteins

Oxidative and Nitrative Modifications of Blood Plasma Proteins in Patients with Myasthenia Gravis

2016 ◽  
Vol 100 ◽  
pp. S166
Author(s):  
Izabela Sadowska-Bartosz ◽  
Sabina Galiniak ◽  
Grzegorz Bartosz ◽  
Izabela Rozmiłowska ◽  
Damian Czyżewski ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Blood Plasma ◽  
Plasma Proteins ◽  
Blood Plasma Proteins

Feracryl, a new hemostatic polymer, and its interaction with blood plasma proteins

1980 ◽  
Vol 14 (7) ◽  
pp. 431-433 ◽  
Author(s):  
V. Z. Annenkova ◽  
N. G. Dianova ◽  
V. M. Annenkova ◽  
G. S. Ugryumova ◽  
M. G. Voronkov
Keyword(s):  
Blood Plasma ◽  
Plasma Proteins ◽  
Blood Plasma Proteins
Sign in / Sign up

Export Citation Format

Share Document