Related Experiment Video

Updated: Jun 26, 2026

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)
06:41

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)

Published on: January 10, 2025

Decrease of dynamin 2 levels in late-onset Alzheimer's disease alters Abeta metabolism

Eiichiro Kamagata1, Takashi Kudo, Ryo Kimura

  • 1Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.

Biochemical and Biophysical Research Communications
|January 8, 2009
PubMed

Insights

Dynamin 2 (DNM2) gene expression is reduced in late-onset Alzheimer's disease (LOAD), leading to increased amyloid precursor protein (APP) accumulation. This suggests a novel mechanism contributing to amyloid beta protein (Abeta) secretion in LOAD neurons.

Area of Science:

  • Neuroscience
  • Genetics

Background:

  • Late-onset Alzheimer's disease (LOAD) is linked to genetic factors, including dynamin 2 (DNM2) gene variations.
  • The apolipoprotein E-epsilon4 allele is a known risk factor, but LOAD also occurs in non-carriers.

Purpose of the Study:

  • To investigate the role of DNM2 in LOAD pathogenesis.
  • To explore the impact of reduced DNM2 expression on amyloid precursor protein (APP) processing and amyloid beta protein (Abeta) secretion.

Main Methods:

  • Real-time PCR to quantify DNM2 mRNA levels in Alzheimer's disease (AD) brain cortex and patient blood.
  • Transfection of neuroblastoma cells with a dominant-negative DNM2 to mimic reduced DNM2 function.
  • Analysis of APP localization and Abeta secretion in transfected cells.

Main Results:

  • DNM2 mRNA levels were significantly decreased in AD brain cortex and dementia patient blood.
  • Cells with reduced DNM2 showed increased Abeta secretion.
  • APP accumulated in the plasma membrane of these cells, particularly in flotillin-rich lipid rafts.

Conclusions:

  • Reduced DNM2 expression is a feature of LOAD.
  • DNM2 deficiency may lead to APP accumulation in lipid rafts, promoting Abeta secretion in neurons.
  • This pathway represents a potential therapeutic target for LOAD.

More Related Videos

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons06:23

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons

Published on: October 30, 2018

Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model06:02

Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model

Published on: July 26, 2011

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...
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...
Dementia l: Introduction01:22

Dementia l: Introduction

Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...