Related Experiment Video
Updated: Aug 15, 2026
15:23
Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease
Published on: May 13, 2010
The amyloid peptide precursor in Alzheimer's disease
1Faculté de Médecine, Laboratoire de Neurochimie, Université Catholique de Louvain.
Acta Neurologica Belgica
|December 1, 1995
Summary
Beta-amyloid (A4) peptide, a key component of Alzheimer's disease (AD) senile plaques, originates from the amyloid precursor protein (APP). Understanding APP processing pathways is crucial for developing AD therapies.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is characterized by senile plaques, primarily composed of beta-amyloid (A4) peptide.
- The A4 peptide is derived from a larger precursor protein, amyloid precursor protein (APP).
- APP gene mutations on chromosome 21 are linked to familial AD (FAD).
Purpose of the Study:
- To elucidate the origin and processing of the beta-amyloid peptide.
- To understand the different metabolic pathways of the amyloid precursor protein.
- To identify potential therapeutic targets for Alzheimer's disease.
Main Methods:
- cDNA cloning and sequencing to characterize APP and its isoforms.
- Overexpression of APP in cultured cells to study its catabolic pathways.
- Analysis of APP gene mutations in familial Alzheimer's disease cases.
Main Results:
- Multiple APP isoforms (365-770 amino acids) are produced via alternative splicing.
- Two main APP catabolic pathways exist: non-amyloidogenic and amyloidogenic.
- The amyloidogenic pathway, involving beta- and gamma-secretases, produces beta-amyloid, which is neurotoxic when fibrillized.
Conclusions:
- APP metabolism is fundamentally involved in Alzheimer's disease pathogenesis.
- Factors promoting beta-amyloid fibril formation are critical risk factors for AD.
- Targeting APP processing, particularly stimulating the non-amyloidogenic pathway, offers therapeutic potential for AD.
Related Concept Videos
03:03Amyloid 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 deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid 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 deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:26Alzheimer'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...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
01:22Alzheimer'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...
01:29Alzheimer 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...
01:23Alzheimer 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...