Lecture 9: Alzeimer's Disease

Question 1

Working memory

Answer 1

• Active manipulation of info
• Also called short-term memory
• Reliant on prefrontal cortex
• Marked decline in elderly

Question 2

Explicit Memory

Answer 2

• Memory with conscious recall eg. facts, knowledge, personal experiences and events
• Regions involved in storage: hippocampus, entorhinal cortex, perirhinal cortex, parahippocampal gyrus, cerebral cortex

Question 3

Episodic Memory

Answer 3

• also known as declarative memories

- most susceptible to brain damage and most affected by ageing

Question 4

Consolidation of declarative memories

Answer 4

• Entorhinal cortex chooses what gets sent to hippocampus
• Hippocampus is then crucial in encoding info -> sent to cortex for storage
• Entorhinal and hippocampus help embed memory and assist in retrieval
• Overtime the memory becomes so well connected in the cortex it can be accessed without the entorhinal and hc

Question 5

Entorhinal and hippocampus with age

Answer 5

• the older the long term memory the less r4eliant it is on these structures to facilitate its recall
• Damage to these regions preferentially affects more recent over older memories
• HC damage -> memory impairments extend back only a few years
• HC and EC -> impaired memory extends back for a longer period

Question 6

Macroscopic Brain Changes

Answer 6

• Atrophy
• Widening of sulci and enlargement of ventricles
• Most pronounced in frontal, temporal and parietal lobes

Question 7

Preclinical AD

Answer 7

• Signs are first noticed in the EC then the HC
• Affected regions shrink as nerve cells die
• Changes can begin 10-20 years before symptoms appear
• Memory loss is the first sign of AD

Question 8

Cholinergic Hypothesis of AD

Answer 8

Deficits in
- Choline acetyltransferase (enzyme responsible for synthesis of ACh)
- Reduced choline uptake and ACh release
- Loss of choinergic neurons from basal forebrian
Acetylcholinesterases inhibs main treatments for AD (stop the bd of ACh)

Question 9

Pathology of AD

Answer 9

• Amyloid beta plaques (extracellular)
• NFT (intracellular)
• WS loss of neurons and synapses

Question 10

A-Beta Toxicity

Answer 10

• Axonal damage
• Synaptic damage
• Excitotoxicity
• Mitochondrial dysfunction

Question 11

NF tangles

Answer 11

• Found in: EC, hippocampus pyramidal cells, amygdala, basal forebrain
• No of tangles correlates better with degree of cognitive decline than no of plaques

Question 12

Types of AD

Answer 12

Sporadic: 75%
- Majority late onset
- Sam symptoms as familial
Familial
- Early onset: 5% and single gene inheritance
- Late onset: 15-25%, complex inheritance

Question 13

Early-Onset AD Genes

Answer 13

Gene: APP
- chromosome 21
Gene: presenilin1 
- chromosome: 14
Gene: presenilin2
- chromosome: 1
- rare
Presenilin mutations increase the cleavage of APP into amyloid-beta

Question 14

Late Onset AD Genes

Answer 14

Gene: ApoE
- chromosome 19
Gene: A2M
- chromosome 12

Question 15

Neuroinflam and AD

Answer 15

• Increase expression of pro-inflam markers
• A-B can attract and activate microglia and astrocytes
• Microglia and astrocytes may also secrete AB

Question 16

Treatment of AD

Answer 16

• No cure, just slow progression and manage symptoms
  Medications for memory loss:
• Mild to moderate AD: cholinesterase inhibitors
• Moderate to severe: memantine (protects brains cells from excess glutamate by preventing reabsorption of the glutamate into neurons)