Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Multidimensional Safety Assessment of a Low-Intensity Scanning Ultrasound (SUS) Protocol in Sheep.

Ultrasound in medicine & biology·2026
Same author

Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice.

Nature communications·2026
Same author

Drug Development.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2025
Same author

A pilot safety and tolerability study of scanning ultrasound as a neuromodulation therapy in Alzheimer's disease.

Brain communications·2025
Same author

Think sepsis, write sepsis, code sepsis - patient characteristics associated with sepsis (under-)coding in administrative health data.

Infection·2025
Same author

Feasibility of ultrasound-mediated blood-brain barrier opening in sheep using sonolucent cranial implants.

Scientific reports·2025

Related Experiment Video

Updated: Jun 26, 2026

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons
10:38

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons

Published on: December 22, 2023

Substrate-specific reduction of PP2A activity exaggerates tau pathology.

Natasha Deters1, Lars M Ittner, Jürgen Götz

  • 1Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.

Biochemical and Biophysical Research Communications
|January 8, 2009
PubMed
Summary

Protein phosphatase 2A (PP2A) inhibition worsens tau pathology in Alzheimer's disease models. Targeting PP2A may offer a new therapeutic strategy for Alzheimer's disease by preventing tau hyperphosphorylation and neurofibrillary tangle formation.

More Related Videos

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
10:46

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models

Published on: May 3, 2017

Related Experiment Videos

Last Updated: Jun 26, 2026

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons
10:38

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons

Published on: December 22, 2023

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
10:46

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models

Published on: May 3, 2017

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Protein phosphatase 2A (PP2A) plays a crucial role in regulating the phosphorylation of the microtubule-associated protein tau.
  • Imbalances in kinase and phosphatase activity lead to tau hyperphosphorylation and the formation of neurofibrillary tangles, a hallmark of Alzheimer's disease.

Purpose of the Study:

  • To investigate the role of PP2A in tau pathology by examining the effects of inhibiting PP2A activity in a mouse model of Alzheimer's disease.

Main Methods:

  • Crossed Dom5 mice, expressing a dominant-negative mutant of PP2A (L309A Calpha), with P301L mutant tau transgenic pR5 mice.
  • Assessed tau phosphorylation at the pathological S422 epitope and quantified neurofibrillary tangle formation in the hippocampus of double-transgenic mice.

Main Results:

  • Double-transgenic Dom5/pR5 mice exhibited a significant exacerbation of tau pathology compared to pR5 mice.
  • A 7-fold increase in hippocampal neurons with pathological S422 tau phosphorylation and an 8-fold increase in neurofibrillary tangles were observed in Dom5/pR5 mice.
  • These findings align with previous observations correlating S422 tau phosphorylation with subsequent tangle formation.

Conclusions:

  • PP2A, in addition to kinases, is a key regulator of tau phosphorylation and neurofibrillary tangle formation.
  • Inhibition of PP2A activity exacerbates tau pathology, suggesting that PP2A and its regulatory subunits are potential therapeutic targets for Alzheimer's disease.