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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...
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...
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...

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Updated: Jun 3, 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

Decrease in brain soluble amyloid precursor protein β (sAPPβ) in Alzheimer's disease cortex.

Guoxin Wu1, Sethu Sankaranarayanan, Sidney H-K Hsieh

  • 1Department of Neurology, Merck Research Laboratory, West Point, Pennsylvania. guoxin_wu@merck.com

Journal of Neuroscience Research
|March 25, 2011
PubMed
Summary
This summary is machine-generated.

Alzheimer's disease (AD) brains show reduced amyloid precursor protein (APP) fragment sAPPβ, despite unchanged BACE1 activity. This suggests reduced APP substrate, not increased BACE1, drives amyloid pathology in late-stage AD.

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Last Updated: Jun 3, 2026

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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

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Alzheimer's disease (AD) is linked to amyloid-β peptide (Aβ) accumulation.
  • Amyloid precursor protein (APP) cleavage by BACE1 and γ-secretase generates Aβ.
  • Increased BACE1 activity is hypothesized to drive AD pathophysiology.

Purpose of the Study:

  • To investigate the relationship between BACE1 activity and endogenous APP processing in AD brains.
  • To directly measure brain sAPPβ levels as an indicator of BACE1 activity in vivo.
  • To clarify the role of BACE1 in Alzheimer's disease pathogenesis.

Main Methods:

  • Developed and utilized a novel APP β-site specific enzyme-linked immunosorbent assay (ELISA).
  • Measured brain cortical levels of sAPPβ, BACE1 activity, full-length APP, sAPPα, and Aβ peptides.
  • Compared these markers in Alzheimer's disease (AD) subjects and control subjects.

Main Results:

  • Significantly reduced brain cortical sAPPβ levels were observed in AD subjects compared to controls.
  • BACE1 enzymatic activity remained unchanged in AD brains.
  • Full-length APP and sAPPα levels were significantly reduced, while Aβ peptides were elevated in AD brains.

Conclusions:

  • Reduced cortical sAPPβ in late-stage AD, coupled with unchanged BACE1 activity, indicates reduced full-length APP substrate availability.
  • These findings challenge the hypothesis of increased BACE1 activity as the primary driver of AD amyloid pathology.
  • Multiparameter analysis is crucial for understanding AD pathophysiology across different disease stages.