Amyloid-β containing isoaspartate 7 as potential biomarker and drug target in Alzheimer's disease

2016 ◽  
Vol 26 (4) ◽  
pp. 269-275 ◽  
Author(s):  
Sergey A. Kozin ◽  
Vladimir A. Mitkevich ◽  
Alexander A. Makarov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Target ◽  
Amyloid Β ◽  
Potential Biomarker

The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

2021 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Diyang Lyu ◽  
Jianping Jia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Dementia Patients ◽  
Positron Emission ◽  
Potential Biomarker ◽  
Synaptic Degeneration ◽  
Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

scholarly journals Nicotinamide as Potential Biomarker for Alzheimer’s Disease: A Translational Study Based on Metabolomics

2021 ◽  
Author(s):  
Maria Carolina Dalmasso ◽  
Martin Aran ◽  
Pablo Galeano ◽  
Silvia Perin ◽  
Patick Giavalisco ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Control Sample ◽  
Amyloid Β ◽  
Rat Plasma ◽  
Preclinical Study ◽  
Blood Collection ◽  
Potential Biomarker ◽  
Nad Synthesis

Abstract Background: The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studiesMethods: We performed untargeted 1H-NMR metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis. Three groups of 9 month-old rats were tested: hemizygous Tg+/-, displaying mild amyloid pathology characterized by intraneuronal amyloid β (iAβ) accumulation; homozygous Tg+/+, showing iAβ, senile plaques and neuroinflammation, and wild-type (WT). The translational potential of these findings was assessed in plasma of participants in the German longitudinal study on Aging, Cognition and Dementia (AgeCoDe), by targeted GC-EI/MS. Results: Eighteen metabolites were detected, three of them showed significant differences among genotypes, but only two were specifically assigned to a known molecule: nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). Only Tg+/+ rats showed significantly decreased levels of total-NAD, NADH and NAD+ as compared to WT, and a significant increase in NAD+/NADH ratio, suggesting an alteration of the redox state, alongside the reduction of all forms of NAD. Transcript levels of NAD-consuming and NAD-synthesis enzymes were increased in both transgenic genotypes. Next, Nam and NAD were evaluated at the peripheral level in rat plasma, where NAD/H was undetectable, Nam levels were unchanged among genotypes, but Trigonelline (a metabolic product of Nam) was reduced in Tg+/+. While trigonelline was undetected, Nam was significantly reduced in AD demented patients respect to cognitively normal participants (controls). This finding in Nam was replicated in a second independent case-control sample drawn from the same AgeCoDe. Next, the predictive value of Nam on disease progression was analyzed. Herein, reduction of Nam levels was observed in AgeCoDe participants who progressed to AD dementia ~1 year after blood collection, whereas Nam level were not reduced in those who converted afterwards. Conclusions: This preclinical study suggests that dysregulation of NAD/Nam depends on cerebral amyloid burden, and support the hypothesis that changes observed in the hippocampus may be detected in plasma. Furthermore, the findings in AgeCoDe points toward the potential use of Nam as plasma biomarker for AD.

scholarly journals Synthesis aided structural determination of amyloid-β(1–15) glycopeptides, new biomarkers for Alzheimer's disease

2014 ◽  
Vol 50 (95) ◽  
pp. 15067-15070 ◽  
Author(s):  
Peng Wang ◽  
Jonas Nilsson ◽  
Gunnar Brinkmalm ◽  
Göran Larson ◽  
Xuefei Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Amyloid Β ◽  
Structural Determination ◽  
Potential Biomarker ◽  
New Biomarkers

The structure of an Aβ glycopeptide is determined, which is a potential biomarker for early diagnosis of Alzheimer's disease.

scholarly journals A conformational variant of p53 (U-p53AZ) as blood-based biomarker for the prediction of the onset of symptomatic Alzheimer’s disease

2021 ◽  
Author(s):  
Simona Piccirella ◽  
Leander Van Neste ◽  
Christopher Fowler ◽  
Colin L Masters ◽  
Jurgen Fripp ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Predictive Performance ◽  
Protein Sequencing ◽  
Imaging Biomarkers ◽  
Plasma Samples ◽  
Ongoing Research ◽  
Potential Biomarker

AbstractBackgroundOngoing research seeks to identify blood-based biomarkers able to predict the onset and progression of Alzheimer’s disease (AD). A potential biomarker is the unfolded conformational variant of p53, previously observed in individuals in the prodromal and clinical AD stages. In this retrospective study, we compare diagnostic and prognostic performances of measures of the amyloid β load with those of a conformational variant of U-p53 in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort.MethodsImmunoprecipitation (IP) followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS) and protein sequencing in plasma samples from the AIBL study identified the clinically relevant AZ 284® peptide, representing a measure of the U-p53 conformational variant (U-p53AZ). Based on U-p53AZ quantification via IP/LC electrospray ionisation-coupled MS/MS (AlzoSure® Predict test) on 515 samples from 482 individuals from the AIBL cohort, the predictive performance of U-p53AZ was assessed and compared with amyloid load as measured by amyloid β-positron emission tomography (Aβ-PET). Its predictive performance was determined at 36, 54, 72 and 90 months following baseline assessment.ResultsU-p53AZ was able to identify individuals with AD dementia with an area under the receiver operating characteristic curve (AUC) of 99%. U-p53AZ outperformed the conventional Aβ-PET measures in predicting the onset of AD dementia both from preclinical (AUC=98%) and prodromal stages (AUC=89%), even 90 months prior to onset (AUC=99%). Additionally, the estimated predictive performance of U-p53AZ was superior (AUC ≥98%) to other risk factors (i.e., gender, Aβ-PET and APOE ε4 allele status) in identifying individuals at high risk for progression to AD.ConclusionThese findings support use of U-p53AZ as blood-based biomarker predicting if individuals, at both asymptomatic and MCI stages, would progress to AD at least six years prior to the onset of clinical AD dementia.

Potential roles of α-amylase in Alzheimer’s disease: Biomarker and drug target

2021 ◽  
Vol 20 ◽  
Author(s):  
Win Ning Chen ◽  
Kim San Tang ◽  
Keng Yoon Yeong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Target ◽  
Specific Activity ◽  
Amyloid Β ◽  
Vital Role ◽  
Amylase Inhibitors ◽  
Insight Into

: Alzheimer’s disease (AD), the most common form of dementia, is pathologically characterized by the deposition of amyloid-β plaques and the formation of neurofibrillary tangles. In a neurodegenerative brain, glucose metabolism is also impaired and considered as one of the key features in AD patients. The impairment causes a reduction in glucose transporters and the uptake of glucose as well as alterations in the specific activity of glycolytic enzymes. Recently, it has been reported that α-amylase, a polysaccharide-degrading enzyme, is present in the human brain. The enzyme is known to be associated with various diseases such as type 2 diabetes mellitus and hyperamylasaemia. With this information at hand, we hypothesize that α-amylase could have a vital role in the demented brains of AD patients. This review aims to shed insight into the possible link between the expression levels of α-amylase and AD. Lastly, we also cover the diverse role of amylase inhibitors and how they could serve as a therapeutic agent to manage or stop AD progression.

scholarly journals Nicotinamide as potential biomarker for Alzheimer’s disease: a translational study based on metabolomics

2021 ◽  
Author(s):  
Maria Carolina Dalmasso ◽  
Martin Aran ◽  
Pablo Galeano ◽  
Silvia Perin ◽  
Patick Giavalisco ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Control Sample ◽  
Amyloid Β ◽  
Rat Plasma ◽  
Blood Collection ◽  
H Nmr ◽  
Potential Biomarker ◽  
Nad Synthesis

Abstract The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. We performed untargeted 1H-NMR metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis. Three groups of 9 month-old rats were tested: hemizygous Tg+/-, displaying mild amyloid pathology characterized by intraneuronal amyloid β (iAβ) accumulation; homozygous Tg+/+, showing iAβ, senile plaques (extracellular Aβ deposition) and neuroinflammation, and wild-type (WT). Eighteen metabolites were detected, three of them showed significant differences among genotypes, but only two were specifically assigned to a known molecule: nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). Only Tg+/+ rats showed significantly decreased levels of total-NAD, NADH and NAD + as compared to WT, and a significant increase in NAD+/NADH ratio, suggesting an alteration of the redox state, alongside the reduction of all forms of NAD. Transcript levels of NAD-consuming (CD38 and PARP2) and NAD-synthesis (NMNAT2) enzymes were increased in both transgenic genotypes. Next, Nam and NAD were evaluated at the peripheral level by targeted 1H-NMR analysis in rat plasma, where NAD/H was undetectable, Nam levels were unchanged among genotypes, but Trigonelline (a metabolic product of Nam) was reduced in Tg+/+. Finally, the translational potential of these findings in the rat model was assessed by measuring Nam and Trigonelline levels in plasma of participants in the German longitudinal study on Aging, Cognition and Dementia (AgeCoDe), by targeted GC-EI/MS. While trigonelline was undetected, Nam was significantly reduced in AD demented patients respect to cognitively normal participants (controls). This finding in Nam was replicated in a second independent case-control sample drawn from the same AgeCoDe. Next, the predictive value of Nam on disease progression was analyzed in AgeCoDe. Herein, reduction of Nam levels was observed in AgeCoDe participants who progressed to AD dementia ~ 1 year after blood collection, whereas Nam level were not reduced in those who converted afterwards. In summary, this preclinical study suggests that dysregulation of NAD/Nam depends on cerebral amyloid burden, and support the hypothesis that changes observed in the hippocampus may be detected in plasma. Furthermore, the findings in AgeCoDe points toward the potential use of Nam as plasma biomarker for AD.

scholarly journals Predictive Potential of Circulating Ube2h mRNA as an E2 Ubiquitin-Conjugating Enzyme for Diagnosis or Treatment of Alzheimer’s Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3398 ◽  
Author(s):  
Key-Hwan Lim ◽  
Jae-Yeol Joo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Brain Diseases ◽  
Clinical Approach ◽  
Potential Biomarker ◽  
Ubiquitin Conjugating Enzyme ◽  
The Brain ◽  
Conjugating Enzyme

Neurodegenerative disorders are caused by neuronal cell death, miscommunications between synapse, and abnormal accumulations of proteins in the brain. Alzheimer’s disease (AD) is one of the age-related disorders, which are the most common degenerative disorders today, and strongly affects memory consolidation and cognitive function in the brain. Amyloid-β and tau proteins are triggers for AD pathogenesis, and usually used as AD candidate biomarkers in the clinical research. Especially, clinical exam, brain imaging and molecular biological methods are being used to diagnosis for AD. Genome-wide association study (GWAS) is a new biomedical method, and its use contributes to understanding many human diseases, including brain diseases. Here, we identified ubiquitin conjugating enzyme E2 (Ube2) gene expression in neurons through GWAS. The subfamilies of Ube2’s genetic expression and inborn errors affect the ubiquitin proteasome system (UPS), leading to protein degradation in the brain. We found that only Ube2h mRNA transcription was significantly increased in the blood from AD, however we did not find any change of Ube2 subfamily genes’ expression in the blood and brain tissue. These data may provide information for diagnosis or clinical approach, and suggest that cell-free circulating Ube2h mRNA is a novel potential biomarker for AD.

Sign in / Sign up

Export Citation Format

Share Document