L9 Flashcards

Question

what is Beta Amyloid (Aβ)

Answer 1

``` Beta Amyloid (Aβ) is produced when APP is cut into segments (cleaved) by secretases. ```

Answer 2

In AD, Beta Amyloid is overproduced. It clumps together and forms fibrillar plaques on the outside surface of cells. these plaques are distributed throughout the cortex and are toxic (they start to kill neurons)

Answer 3

because AAP is usually cleaved by alpha scrotase at the part of the protein which would become the middle of Aβ getting cleaved in the middle of Aβ means that it wouldn't never be able to form

Answer 4

beta and gamma secretase cleave AAP in a way that Aβ is formed

Answer 5

Amyloid Plaque location doesn’t map well onto symptoms therefore when you look at the distribution of Aβ and where they are damaging in the brain it doesn't add up to what the symptoms of AD are

Answer 6

New drug that has just received FDA approval for treatment of AD What it is effective in is removing the plaques from the brain but removing these doesn't appear to have any effect on the cognition of the individuals

Answer 7

they hold the microtubules together it their tubal structure

Answer 8

Microtubules are the scaffold of the neurons. What happens in AD is the the Tau protein gets phosphorylated and the tou forms clumps inside the cell called neurofibrillary tangles (NFTs) You then have a disruption in the microtubules as they fall apart and no longer make connections with other neurons This degeneration does map well with the symptoms

Answer 9

neurofibrillary tangles (NFTs)

Answer 10

As Alzheimer’s progresses NFTs appear initially in the transentorhinal (perirhinal) cortex. this is where information from the cortex goes into the hippocampus As the disease progresses then the tangles start to go into the hippocampus and then in neighbouring regions. NFT progression parallels cognitive deficits

Answer 11

the more NFTs you have the worse cognitive impairments you have on a Mini mental state exam

Answer 12

age (5% < 65 years) Family history/genetic disposition - People with relatives who developed Alzheimer's disease are more likely to develop the disease themselves. Familial (early onset) - only makes up 2-3% of cases BUT if someone in your family has it it increases your likelihood by 50% chance for early onset

Answer 13

linked to mutation on PSEN1, PSEN2, APP genes

Answer 14

when you see symptoms before 65

Answer 15

risk is related to variations of the APOE gene on chromosome 19

Answer 16

There are three major variations (alleles) of the APOE gene- called APOE2, APOE3 and APOE4. We are each born with two alleles at the APOE gene that we inherit from our parents. We can have any combination of the three variations. Having one E4 confers 2-3 x higher risk Having E4/E4 confers 5-8 x higher risk

Answer 17

These APOE gene alleles produce slightly different forms of the Apolipoprotein E (ApoE) protein. ApoE is mainly produced by astrocytes, and transports cholesterol to neurons

Answer 18

i'm not sure theres a graph in the lecture but IDK what it wants from me

Answer 19

reduction in APOE level causing cholesterol accumulation and impaired beta amylase clearance

Answer 20

they become immune prone (over reactive) and have impaired beta amylase clearance

Answer 21

increased synapps formation elevated rely endosomes increases formation of beta amylase

Answer 22

The BBB separates the circulation from the brain, allowing for protection from and transport regulation of serum factors and neurotoxins. ``` The BBB is not just a physical barrier but also acts more selectively as a transport interface, a secretory body, and a metabolic barrier (containing and releasing certain enzymes locally) ```

Answer 23

The gene variant APOE4 is associated with a disruption of tight junctions, which opens up the BBB APOE4 was associated with higher BBB permeability in hippocampus and parahippocampal gyrus – independent of amyloid and Tau accumulation

Answer 24

then endothelial cells are held together via tight junctions the capillaries is also covered by astrocytes for support and then pericytes for maintaining that support

Answer 25

the BBB is leaky which leads to elevated levels of a marker for pericyte injury predicts cognitive decline

Answer 26

you see the first cognitive symptoms after 1-2 years (therefore it is developing for about 1-2 years before you get a diagnosis)

Answer 27

The University of Minnesota ‘Nun Study’ is a longitudinal study of aging and Alzheimer's disease. Participants were 678 American members of the School Sisters of Notre Dame religious congregation who were aged 75 to 102 years of age .

Answer 28

because early life autobiographies were obtained at average age 22 They had been in this order for a long period of time. They have had the same diet and the same environmental exposure because they have lived in the nunnery since that were 20

Answer 29

The more ideas they had when they were 20 years old the less likely they were to develop AD therefore this suggests that the things you did in your 20s has an effect on if you were developing AD Therefore we believe that having a good education protects you from AD (more ideas)

Answer 30

that education is a protective factor against AD

L9 Flashcards

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