Alzheimer's Disease and Mild Cognitive Impairment are Associated with Elevated Levels of Isoaspartyl Residues in Blood Plasma Proteins

2011 ◽  
Vol 27 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Hongqian Yang ◽  
Yaroslav Lyutvinskiy ◽  
Hilkka Soininen ◽  
Roman A. Zubarev
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Blood Plasma ◽  
Plasma Proteins ◽  
Blood Plasma Proteins ◽  
In Blood Plasma

scholarly journals MACHINE LEARNING MODEL BASED ON A PANEL OF PLASMA PROTEINS PREDICTS PROGRESSION FROM MILD COGNITIVE IMPAIRMENT TO DEMENTIA DUE TO ALZHEIMER’S DISEASE WITHIN FOUR YEARS

2021 ◽  
Author(s):  
Daniella Araujo ◽  
Paulo Caramelli ◽  
Nivio Ziviani ◽  
Karina Gomes ◽  
Adriano Veloso ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Plasma Proteins ◽  
Risk Model ◽  
Disease Stage ◽  
Lifestyle Interventions ◽  
Increased Risk

Background: Alzheimer’s disease (AD) is a pathological process that begins many years prior to the emergence of symptoms. Thus, an effective risk model for AD should aim at detecting at-risk individuals in the prodromal stage, when treatments and lifestyle interventions are more likely to be successful, and should be minimally invasive and inexpensive to allow widespread applicability. Objectives: To develop a machine learning based blood panel in individuals with mild cognitive impairment (MCI) to predict increased risk for progression to AD dementia. Methods: We created over one billion models to predict the probability of conversion from MCI to dementia due to AD, and chose the best performing one. We used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data of 380 MCI individuals in the baseline visit, from which 177 converted to AD dementia. Results: The best performing model uses 12 plasma proteins (out of 146 possibilities), giving an average AUC of 0.91, accuracy of 0.92, sensitivity of 0.97 and specificity of 0.85. Conclusions: We were able to predict AD dementia conversion within four years in MCI individuals, a disease stage in which treatments and lifestyle interventions are more likely to be successful. Further studies in independent cohorts are needed to validate this panel.

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.

Blood Plasma IgG Fc Glycans are Significantly Altered in Alzheimer's Disease and Progressive Mild Cognitive Impairment

2013 ◽  
Vol 38 (3) ◽  
pp. 567-579 ◽  
Author(s):  
Susanna L. Lundström ◽  
Hongqian Yang ◽  
Yaroslav Lyutvinskiy ◽  
Dorothea Rutishauser ◽  
Sanna-Kaisa Herukka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Blood Plasma

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

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.

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