Related Experiment Video

Updated: Jun 10, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP

Orso Bugiani1, Giorgio Giaccone, Giacomina Rossi

  • 1Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11-20133, Milan, Italy.

Archives of Neurology
|August 11, 2010
PubMed

Insights

Hereditary cerebral hemorrhage with amyloidosis linked to the APP E693K mutation causes stroke and cognitive decline. This study confirms the APP E693K mutation

Area of Science:

  • Neurology
  • Genetics
  • Pathology

Background:

  • Hereditary cerebral hemorrhage with amyloidosis (HCHWA) is a group of rare genetic disorders.
  • Amyloid precursor protein (APP) mutations are known causes of HCHWA.
  • The APP E693K mutation's role in HCHWA requires further investigation.

Purpose of the Study:

  • To investigate the clinical, genetic, neuroimaging, and neuropathologic features of HCHWA patients with the APP E693K mutation.
  • To establish the genotype-phenotype relationship in families with this mutation.

Main Methods:

  • Case series study involving 37 individuals from 4 Italian families.
  • Clinical data and laboratory results were collected through direct evaluation and medical records.
  • DNA analysis and neuropathologic examination of 2 subjects were performed.

Main Results:

  • Patients presented with recurrent headaches, multiple strokes, epilepsy, and cognitive decline.
  • The disease followed an autosomal dominant inheritance pattern and segregated with the APP E693K mutation.
  • Neuroimaging revealed various types of cerebral bleeding and infarcts; amyloid-beta was found in vessel walls, but not tau pathology.

Conclusions:

  • The APP E693K mutation is associated with hereditary cerebral hemorrhage with amyloidosis.
  • This finding expands the spectrum of APP mutations causing HCHWA.
  • Codon 693 of APP is strongly implicated in the pathogenesis of this phenotype.
Abstract

More Related Videos

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain10:08

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke09:45

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Published on: March 22, 2016

Related Concept Videos

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 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...
Hemorrhagic Stroke l: Introduction01:17

Hemorrhagic Stroke l: Introduction

A hemorrhagic stroke is an acute neurological event that occurs when a weakened cerebral blood vessel ruptures, allowing blood to accumulate within or around the brain. The sudden release of blood forms a focal hematoma that increases intracranial pressure, displaces neural tissue, and can obstruct cerebrospinal fluid pathways. These effects may be compounded by intraventricular extension of the hemorrhage, cerebral edema, or compression of adjacent structures, all of which contribute 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...
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...