Neurotrophic and Neurotoxic Effects of Amyloid Protein: Reversal by Tachykinin

1
Neurotrophic and Neurotoxic Effects of Amyloid ß
Protein Reversal by Tachykinin
Original 1

• Cameron Thomas

2
Amyloid Hypothesis
Original 2

• Proposed 1991

3
Original 3

• Is Amyloid Beta (Aß) the primary component of
  Alzheimer's disease?

4
Plaques
Original 4
5
The effects of Aß in undifferentiated and mature
nerons
Original 5
6
Alzheimers Disease
New 1
7
Alzheimers Disease
New 2

• Most common cause of dementia

8
Alzheimers Disease
New 3

• Most common cause of dementia

• Clue Associated with plaques and tangles

Tangles
Plaques
Dennis Selkoe, selkoelab.bwh.harvard.edu
9
Alzheimers Disease
New 4

• Most common cause of dementia

• Clue Associated with plaques and tangles

• Plaques Aggregates of single protein, Ab,
  derived from APP (Amyloid Precursor Protein)

Tangles
Ab
APP
AggregatedAb
Plaques
Dennis Selkoe, selkoelab.bwh.harvard.edu
10
Alzheimers Disease
New 5

• Most common cause of dementia

• Clue Associated with plaques and tangles

• Plaques Aggregates of single protein, Ab,
  derived from APP (Amyloid Precursor Protein)

Ab
Cause of AD?
AggregatedAb
Plaques
11
Alzheimers Disease
New 6
Does Ab peptide induce neurotoxicity?
Ab
Cause of AD?
AggregatedAb
Plaques
12
Details of Experiment
Original 6

• Amyloid Beta protein (B140)
• Hippocampal cells
• Control vs B1-40 treated.
• 20 µm

13
How to assess role of Ab protein?
New 7

• Grow healthy hippocampal cells

5 Days
14
How to assess role of Ab protein?
New 8

• Grow healthy hippocampal cells

• Add Ab protein

5 Days
hippocampus
15
How to assess role of Ab protein?
New 9

• Grow healthy hippocampal cells

• Add Ab protein

• Count live neurons

Neuron-specificantibody
5 Days
hippocampus
16
Original 7
Control
Treated
17
New 10
Does Ab protein induce neurotoxicity?
No Ab protein
Ab protein
Neurotrophic
Neurotoxic
18
Amyloid ß shows neurotoxic effects
Original 8
19
References
Original 9

• Yankner B. A., Duffy L. K., Kischner D. A.
  (1990). Neurotrophic and Neurotoxic Effects of
  Amyloid ß Protein Reversal by TachykininNeuropept
  ides. Science, 250(4978), 279-82