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Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
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...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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...

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Related Experiment Video

Updated: May 8, 2026

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
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High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment

Published on: July 18, 2017

CD33 Alzheimer's risk-altering polymorphism, CD33 expression, and exon 2 splicing.

Manasi Malik1, James F Simpson, Ishita Parikh

  • 1Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 16, 2013
PubMed
Summary

Alzheimer's disease risk is linked to a CD33 gene variation (rs12459419) affecting microglial function through RNA splicing. This finding offers new therapeutic targets for Alzheimer's disease.

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Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
04:41

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration

Published on: January 9, 2020

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Genome-wide association studies (GWAS) identify novel Alzheimer's disease (AD) risk factors.
  • Understanding the functional mechanisms of these genetic polymorphisms is crucial for validating findings and developing therapeutic strategies.
  • CD33, a sialic acid-binding Ig-superfamily lectin (SIGLEC), is implicated in AD pathogenesis.

Purpose of the Study:

  • To elucidate the mechanism of action of the AD-associated polymorphism rs3865444 in the promoter of the CD33 gene.
  • To identify the functional single nucleotide polymorphism (SNP) responsible for modulating CD33 expression and function in AD.
  • To propose a novel model for how SNP-modulated RNA splicing influences CD33 function and AD risk.

Main Methods:

  • Immunohistochemistry to determine CD33 expression in human brain microglia.
  • Correlation analysis of CD33 mRNA expression with microglial markers and AD status.
  • Analysis of CD33 isoforms and sequencing of the CD33 gene from promoter through exon 4.
  • Minigene RNA splicing assays in BV2 microglial cells to assess the functional impact of identified SNPs.

Main Results:

  • CD33 is expressed in human brain microglia, with expression correlating with microglial markers and modestly increasing with AD status and the rs3865444C AD-risk allele.
  • A common CD33 isoform (D2-CD33) lacking exon 2 was identified, and its proportion correlated with rs3865444 genotype.
  • A functional SNP, rs12459419 in exon 2, was identified and shown to modulate CD33 exon 2 splicing efficiency.
  • rs3865444 acts as a proxy SNP for rs12459419, indicating that this polymorphism influences AD risk via altered CD33 splicing.

Conclusions:

  • CD33 is a microglial gene, and its expression and splicing are modulated by specific genetic variations.
  • The AD risk polymorphism rs3865444 is linked to rs12459419, which functionally alters CD33 splicing.
  • SNP-modulated RNA splicing of CD33 represents a novel mechanism influencing Alzheimer's disease risk, potentially offering new therapeutic targets.