Alzheimer's Pathophysiology

Question 1

What is the main basic of Alzheimers?

Answer 1

Loss of neurons and synapses in the cerebral cortex and certain subcortical regions - gross atrophy, loss of or shrinking off mass.

Question 2

What is a neuron?

Answer 2

A communicating cell, electronically excitable that transmits information through electrical and chemical signals

Question 3

What is a synapse?

Answer 3

The area before, including and immediately after a ‘cleft’ or gap between two neurones that allows communication between two neurons via signals

Question 4

What is the cerebral cortex?

Answer 4

The outermost structure of tissue of the cerebrum

Question 5

What are the two causes of pathology in a case of alzheimers disease?

Answer 5

amyloid plaques and tau tangles

Question 6

What is an amyloid plaque?

Answer 6

Insoluble fibrous protein aggregate sharing specific structural traits - innappropriately folded versions of proteins and polypeptides that are present naturally in the body.

Question 7

What is the form of amyloid plaque in alzheimers?

Answer 7

Beta-amyloid. Dense, insoluble deposits of Ab peptide and cellular materials outside and around neurons.

Question 8

What is beta amyloid (Ab)?

Answer 8

A result of APP being proteolysed.

Question 9

What is APP?

Answer 9

Amyloid Precursor Protein. An integral membrane protein expressed in many tissues, concentrated in the synapses of neurones. Normal functions include regulating synapse function, neural plasticity and iron export, growth/survival and post injury repair.

Question 10

How do Ab cause disease?

Answer 10

Not ENTIRELY KNOWN. Accumulation of Ab thought to trigger neural degeneration. The toxic form of the protein is responsible for disrupting cells calcium ion homeostasis, inducing apoptosis.

Question 11

Where does Ab build up?

Answer 11

In the mitochondria of AD brain cells, inhibiting enzyme function and utilization of glucose by neurones

Question 12

What else does Ab do?

Answer 12

Instigates cytokine and inflammatory molecule action, causing damage.

Question 13

What are the four stages of dementia called?

Answer 13

Pre-dementia, early, moderate and advanced.

Question 14

What is a sign of pre-dementia?

Answer 14

Often mistaken for stress and ageing - mild cognitive difficulties like apathy and depression

Question 15

What is a sign of early AD?

Answer 15

increased impairment of cognitive function, learning/memory

Question 16

What is a sign of moderate AD?

Answer 16

Independance hindering deterioration, speech/reading/writing/complex motor sequences

Question 17

What is a sign of advanced AD?

Answer 17

dependence on caregivers, apathy, exhaustion, only knows simple phrases/words, death from 2’

Question 18

What is the link between downs and AD?

Answer 18

People with downs get AD at about 40, universally because the APP is coded for on chrom 21, the gene they have twice.

Question 19

What is the link between APOE4?

Answer 19

Apolipoprotein isoform malfunctioning by not clearing Ab, leading to increased amyloid buildup.

Question 20

Average life expectancy post-diagnosis?

Answer 20

7 years, less than 3% live past 14 years

Question 21

what is the average age of onset?

Answer 21

65

Question 22

What is the structure of APP?

Answer 22

The extracellular part has 2 domains, E1 and E2, E1 has two subdomains, the copper binding domain and the growth like factor domain, E1 and E2 are linked by AcD, an acidic domain

Question 23

Where is the APP gene located?

Answer 23

chromosome 21