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Related Concept Videos

Alzheimer's Disease: Overview01:26

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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
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Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
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Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
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Related Experiment Video

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Biochemical Purification and Proteomic Characterization of Amyloid Fibril Cores from the Brain
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Subcellular proteomics insights into Alzheimer's disease development.

Zhiyuan Liang1, Hongbin Zhuang1, Xueshan Cao1,2

  • 1College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, P. R. China.

Proteomics. Clinical Applications
|August 31, 2023
PubMed
Summary

Proteomics reveals key molecular changes in Alzheimer's disease (AD) pathogenesis, including mitochondrial dysfunction and protein aggregates. This research aids in identifying new biomarkers and therapeutic targets for AD.

Keywords:
Alzheimer's diseaseamyloid plaquesexosomeextracellular vehiclesneurofibrillary tanglesubcellular proteomics

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Proteomics

Background:

  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder with increasing prevalence.
  • Current understanding of AD molecular mechanisms and effective treatments remains limited.
  • Proteomics offers a comprehensive approach to investigate AD pathogenesis.

Purpose of the Study:

  • To review the application of mass spectrometry (MS)-based proteomics in understanding Alzheimer's disease.
  • To focus on subcellular proteomics studies of AD, including mitochondria, synapses, and protein aggregates.
  • To highlight the potential of proteomics for identifying AD biomarkers and drug targets.

Main Methods:

  • Utilizing mass spectrometry (MS)-based unbiased proteomics.
  • Analyzing protein changes in subcellular components: mitochondria, synapses, myelin, amyloid plaques (APs), neurofibrillary tangles (NFTs), extracellular vesicles (EVs), exosomes, ribosomes, and lysosomes.
  • Reviewing sample separation, preparation, and proteomic analysis techniques.

Main Results:

  • Proteomics studies have elucidated AD-associated mitochondrial dysfunction, synaptic damage, and myelin breakdown.
  • Analysis of protein composition in amyloid plaques and neurofibrillary tangles provides insights into AD pathology.
  • Changes in extracellular vesicles, exosomes, ribosomes, and lysosomes reveal further molecular alterations in AD.

Conclusions:

  • Proteomics provides critical insights into the molecular mechanisms underlying Alzheimer's disease pathogenesis.
  • These findings offer a theoretical foundation and direction for future AD research.
  • Proteomic data can significantly aid in the discovery of novel biomarkers and therapeutic targets for AD.