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Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

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. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils03:03

Amyloid Fibrils

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. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Cerebral Edema ll: Pathophysiology01:22

Cerebral Edema ll: Pathophysiology

Vasogenic edema is a major form of cerebral edema characterized by abnormal accumulation of fluid in the brain’s extracellular space due to disruption of the blood–brain barrier (BBB). The BBB is a specialized structure composed of endothelial cells connected by tight junctions, supported by astrocytic endfeet and a basement membrane. Under normal conditions, it tightly regulates the movement of ions, proteins, and solutes between the bloodstream and brain parenchyma. When this barrier loses...
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Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...

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Related Experiment Video

Updated: Jun 12, 2026

Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
09:31

Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry

Published on: March 7, 2019

Circulating neprilysin clears brain amyloid.

Yinxing Liu1, Christa Studzinski, Tina Beckett

  • 1Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, Lexington, KY 40536-0509, USA.

Molecular and Cellular Neurosciences
|June 19, 2010
PubMed
Summary
This summary is machine-generated.

Neprilysin (NEP) therapy effectively reduces amyloid-beta plaques in the brain by increasing its presence in plasma. This approach offers a novel therapeutic strategy for Alzheimer's disease, impacting amyloid transport across the blood-brain barrier.

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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

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Related Experiment Videos

Last Updated: Jun 12, 2026

Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
09:31

Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry

Published on: March 7, 2019

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus
08:16

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus

Published on: June 17, 2015

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
10:08

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) plaque accumulation in the brain.
  • Neprilysin (NEP) is a peptidase known to degrade Abeta.
  • Peripheral NEP expression has previously shown potential in lowering brain Abeta burden.

Purpose of the Study:

  • To investigate the efficacy of a soluble, secreted form of NEP (secNEP) delivered via adeno-associated virus (AAV8) in clearing brain Abeta.
  • To determine if plasma-expressed NEP can reduce both soluble and insoluble Abeta species and oligomers.
  • To assess the safety and mechanism of action of secNEP-AAV8 therapy.

Main Methods:

  • Adeno-associated virus serotype 8 (AAV8) was used to deliver a gene for a soluble, secreted form of NEP (secNEP).
  • Mice were treated with secNEP-AAV8, and NEP expression in plasma was monitored over 3 months.
  • Levels of plasma and brain Abeta (soluble, insoluble, oligomers), substance P, bradykinin, and blood pressure were measured.

Main Results:

  • Sustained NEP expression in plasma was achieved over the 3-month study period.
  • Secreted NEP significantly reduced plasma Abeta by 30%, soluble brain Abeta by 28%, and insoluble brain Abeta by 55%.
  • Abeta oligomers were reduced by 12%, with no significant changes in plasma substance P or bradykinin, or blood pressure. No NEP was detected in cerebrospinal fluid (CSF) or brain tissue.

Conclusions:

  • Plasma-based delivery of NEP using secNEP-AAV8 is effective in reducing brain Abeta burden in a mouse model of AD.
  • The therapeutic effect is mediated by altered blood-brain Abeta transport dynamics, not direct brain NEP expression.
  • Monitoring plasma NEP activity provides a practical method for assessing therapeutic efficacy during treatment.