Related Experiment Video

Updated: Jun 3, 2026

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
11:29

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

Published on: October 3, 2012

Amyloid-beta42 interacts mainly with insoluble prion protein in the Alzheimer brain

Wen-Quan Zou1, Xiangzhu Xiao, Jue Yuan

  • 1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. wenquan.zou@case.edu

The Journal of Biological Chemistry
|March 12, 2011
PubMed

Insights

Prion protein (PrP) interacts with amyloid-beta (Aβ42) in Alzheimer disease (AD) brains. Insoluble PrP (iPrP) is the main form binding to Aβ42, suggesting a role in AD pathogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Prion protein (PrP) is primarily linked to prion diseases.
  • Emerging evidence suggests a potential role for PrP in Alzheimer disease (AD) pathogenesis.
  • PrP's interaction with amyloid-beta (Aβ42) oligomers is a key area of investigation in AD.

Purpose of the Study:

  • To investigate the in vivo interaction between aggregated prion protein (PrP) and amyloid-beta (Aβ) in Alzheimer disease (AD) brain extracts.
  • To identify specific binding sites on PrP for Aβ oligomers.
  • To determine the role of insoluble PrP (iPrP) in Aβ42 interactions.

Main Methods:

  • Co-purification of aggregated human PrP (huPrP) and Aβ42 from AD brain extracts.
  • Immunoprecipitation using anti-PrP antibodies and iPrP-specific agents to co-precipitate insoluble Aβ.
  • Peptide membrane arrays to map Aβ binding sites on huPrP.

Main Results:

  • Aggregated huPrP and Aβ42 were co-purified from human AD brain samples.
  • Insoluble Aβ was co-precipitated with insoluble PrP (iPrP) using specific antibodies and agents.
  • Two distinct Aβ binding sites on huPrP were identified: one specific for Aβ42 (in the octapeptide repeat region) and another binding both Aβ42 and Aβ40 (in N-terminal/C-terminal domains).

Conclusions:

  • Insoluble PrP (iPrP) is the predominant form of PrP interacting with insoluble Aβ42 in the Alzheimer disease brain.
  • This study provides in vivo evidence for the interaction between PrP and Aβ42 in AD.
  • The pathophysiological significance of the iPrP/Aβ42 interaction in AD requires further investigation.

More Related Videos

Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain09:35

Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain

Published on: October 24, 2017

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis06:17

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis

Published on: May 22, 2018

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...
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...
Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

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.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Alzheimer's Disease: Treatment01:22

Alzheimer's Disease: Treatment

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...