Biological Basis of Downs Syndrome and Alzheimers Disease - PowerPoint PPT Presentation

Loading...

PPT – Biological Basis of Downs Syndrome and Alzheimers Disease PowerPoint presentation | free to view - id: 5e717-ZDc1Z



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Biological Basis of Downs Syndrome and Alzheimers Disease

Description:

Biological Basis of Downs Syndrome and Alzheimer's Disease. Trevor Phinney. Alex Hansler ... other downstream caspases that have direct effects on cell death ... – PowerPoint PPT presentation

Number of Views:115
Avg rating:3.0/5.0
Slides: 19
Provided by: alexha4
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Biological Basis of Downs Syndrome and Alzheimers Disease


1
Biological Basis of Downs Syndrome and
Alzheimers Disease
  • Trevor Phinney
  • Alex Hansler

2
Alzheimers Disease
  • Neurodegenerative disease that appears in the
    later periods of life
  • Age of onset between 40-90 years old
  • Leading cause of cognitive dysfunctions
  • Memory loss
  • Dementia
  • Deterioration of language fcuntions

3
Biological Basis of AD
  • Increased Beta-amyloid deposits
  • Derived from App (amyloid precursor protein)
  • Neurofibrillary tangles
  • Increases in caspase activity
  • Decreases in drebrin levels
  • Presenilin Gene (PS-1) mutations
  • ApoE gene

4
Presenilin Gene
  • Austosomal Dominant
  • PS-1 and PS-2
  • Structurally similar
  • 40 mutations of PS-1 gene
  • Only 2 mutations in PS-2
  • On chromosome 14

5
Presenilin Gene(cont)
  • PS-1 mutations lead to early onset AD symptoms
  • Initially 70 of early-onset AD was a result of
    PS-1 mutation, but this is now considered an
    overestimate
  • It is still a major locus for autosomal dominant
    AD mutations
  • PS-2 lead to later onset AD
  • PS-1 mutations are more common than both PS-2 or
    App mutations

6
Apolipoprotein E (ApoE)
  • ApoE is located on chromosome 19
  • Binds to the beta-amyloid (AB) peptide (main
    component of neuritic plaques)
  • It is present in senile plaque
  • Indicates role as a possible pathological
    chaperone
  • It has three common alleles (? 3, 4, 2)
  • Have an effect on the age of onset
  • Not know is loss or gain of function of ApoE that
    influences AD

7
Downs Syndrome
  • Trisomy 21
  • Extra 21st chromosome due to non-disjunction
  • Most frequent cause of mental retardation
  • 1 out of 800 live births
  • Associated with lower levels of cognitive and
    language functioning

8
Biological Hypothesis of Both AD DS
  • Increased Beta-amyloid (AB) deposits
  • Neurofibrillary tangles
  • Increases in caspase activity
  • Causes neuronal cell death (apoptosis)
  • Leads to increases in Beta-amyloid
  • Drebrin abnormalities

9
Beta-Amyloid (AB)
  • Core protein of neuritic plaques
  • Derived from a transmembrane glycoprotein,
    amyloid B precursor protein (APP)
  • APP gene is located on the 21st chromosome
  • DS has three 21st chromosome so the APP level is
    increased
  • No correlation between the amount of AB and the
    severity of the phenotype

10
Plaques
  • Caused by the presence of accumulation of
    beta-amyloid in association with ApoE
  • Three types
  • Neuritic- radial fashion plaques surrounded by
    abnormally found dendrites and axons
  • Diffuse plaques- more spread out deposits of AB
  • End-stage plaques- remnants of old plaques

11
Neurofibrillary Tangles (NFT)
  • Parallel aggregates of thicken fibrils wound in a
    helical fashion
  • Frequently surround the nucleus and extent
    towards apical dendrite
  • Ghost tangles are seen that do not associate
    with any neurons
  • Believed to be indicative of neurons that have
    already died from NFTs

12
Neurofibrillary Tangles (cont)
  • Microtubule associated protein Tau
  • Primary constituent of the NFTs

13
Caspases
  • Only activated during Apoptosis
  • Activation indicates presence of programmed cells
    death
  • Cleaves proteins

14
Caspases (cont)
  • Caspase-8 play initiator role in apoptosis
  • Appears to activate other downstream caspases
    that have direct effects on cell death
  • Caspace activity has been found to be related to
    AB deposition
  • May account for accumulation of AB
  • May also contribute to the formation of NFTs

15
Drebrin
  • Closely related to the development of the brain
  • Found in dendritic spines
  • Associated with microtubules and may aide in
    growth of nueronal projections
  • Expression levels of drebrin decreased in AD and
    DS patients
  • Reduced in temporal and frontal cortex
  • Not significantly reduced in the cerebellum

16
Drebrin (cont)
  • Reduction may lead to disorganization of actin
    filament dynamics and perhaps apoptosis
  • Decreases cause abnormalities in dendritic
    spines of neurons

17
Correlation between AD and DS
  • Individuals with DS develop AD like brain
    abnormalities we discussed after the age of 40
  • Increased Beta-amyloid (AB) deposits
  • Neurofibrillary tangles
  • Increases in caspase activity
  • Drebrin abnormalities
  • Studies of young vs. old DS patients
    distinguished it was an age effect

18
How is this information useful?
  • You can test a middle aged brain for increased AB
    deposits/caspase activity/decreased drebrin/etc.
    to determine likelyhood of developing AD.
  • This shows neuroplasticity in the brain
  • DS patients dont exhibit biological markers
    until after the age of 40
About PowerShow.com