Alzheimer's disease

Question 1

True or False

The central dogma can have modifications in DNA, mRNA, or Protein that can affect the Transcription or Translation rates.

Answer 1

True

Question 2

Match the following terms

(pre-mRNA / introns / exons / RNA splicing / mature RNA )

_______ RNA is transcribed from DNA initially.

_____ Section that remain in RNA

_____ Section that are removed in RNA

______ The process of removal of sections in RNA

________ Final Product of RNA

Answer 2

pre-mRNA

Exons

Introns

RNA splicing

Mature RNA

Question 3

True or False

Multiple exons allow for the possibility of alternative splicing (the inclusion of different exons in mature mRNA) that results in different protein isoforms (variants).

Answer 3

True

Question 4

Proteins can be altered after their biosynthesis through ________________

What are the two main categories of these PTMs?

Answer 4

Post-translational modifications

Reversible and irreversible

Question 5

What are the common reversible and irreversible modifications that a protein can undergo?

Answer 5

Phosphorylation and dephosphorylation are common reversible modifications

Protein cleavage is a common irreversible modification

(a mechanism that quickly activate an enzyme)

Question 6

True or False

Protein function is independent of proteins bring in the right place.

Answer 6

False

Protein function is dependent on proteins being in the right place. (Protein targeting)

Many of the common organelles with cells are involved in protein targeting.

Question 7

The length of axons poses a challenge for protein targeting in neurons. Proteins are synthesized in cell bodies, so how do they transport at great distances along the axon?

Answer 7

Transport along axons is mediated by microtubules.

Molecular motors made out of protein kinesin allow anterograde transport (forward movement)

” “ those made out of protein dynein allow retrograde transport (backward movement)

Question 8

True or False

Protein-mediated toxicity leads to cell death in both Huntington’s disease and Parkinson’s disease.

This reinforces the importance of understanding proteostasis (homeostatic regulation of protein synthesis, folding, modification, targeting, and degradation) for neurodegenerative disorder.

Answer 8

True

Question 9

What are the first signs and symptoms of Alzheimer’s disease?

Answer 9

Mild cognitive impairment (MCI)

(noticeable cognitive decline beyond expectations from normal aging while individuals have preserved activities of daily living)

Question 10

What does mild cognitive impairment often lead to?

Answer 10

Dementia

(impairment in thinking and memory)

Question 11

True or False

Alzheimer’s can occur as familial or spordaic. Most cases are sporadic.

Answer 11

True

Question 12

What are the two distinguishing features of neuropathology that are associated with Alzheimer’s disease?

Answer 12

Amyloid plaques (a.k.a. senile plaques)

Neurofibrillary (tau) tangles

Question 13

________________ are extracellular aggregates of amyloid beta within brain gray matter, and they often aslo contain degenerative neural structures and glia.

________________ are intracellular aggregates of tay protein in cell bodies, dendrites, and axons.

Answer 13

Amyloid plaques

Neurofibrillary tangles

Question 14

__________________ is a transmebrane protein with high abundance at the synapose. It is the precorusor of amyloid beta

Answer 14

Amyloid precursor protein (APP)

Question 15

True or False

APP has multiple points of cleavage near AB.

an alpha site near the middle of AB

a beta site on the N-terminal side of AB

a gamma site on the C-terminal side

The production of AB depends on the order of cleavage

Cleavage is mediated by membrane-bound enzymes called secretases. Only occur when APP is bound to the membrane

Answer 15

All true

Question 16

If alpha-secretase cuts the alpha site first, AB is (never/formed) and (do/do not) contain isoforms.

If beat-secretase cuts the beta site first hollowed by gamma-secretase on the gamma site, AB is (never/formed), and (do/do not) contains isoforms.

If gamma-secretase cuts either gamma -40 or -42 site, AB is (never/formed) and (do/do not) contain isoforms.

Answer 16

never ; do not

fomred ; do not

dormed ; do

AB-40 and AB-42(most toxic)

Question 17

Choose the best option

(AB-40 / AB -42)

Tends to form protein aggregates

Oligomerization through beta-sheet bonding between multiple Ab-42 segements

Answer 17

AB-42

Question 18

Point mutations of APP can alter the risk for Alzheimer’s and even cause Alzheimer’s with autosomal domain case and full penetrance.

Mutations can be considered in three categories, depending on proximity to alpha, beta, and gamma.

Mutations that increase the risk of Alzheimer’s near the ___ cleavage site tend to do so by increasing the chances of ___ cleavage.

Mutations that increase the risk of Alzheimer’s near the ___ cleavage site tend to do so by increasing the chances of ___ cleavage creating Ab-42 rather than AB-40.

Mutations that increase the risk of Alzheimer’s near the ___ cleavage site tend to do so by promoting AB oligomerization after AB is formed.

Answer 18

Beta

gamma ; gamma-42

alpha

Question 19

True or False

Mutations in the secretases increase changes of gamma-42 cleavage creating AB-42 rather than AB-40.

Answer 19

True

Question 20

________________- is a class of proteins involved in the transport and break down of molecules in the blood, especially fats and cholesterol. Common alleles are E2, E3, E4. Exerts large effects on Alzheimer’s risk, perhaps through a role in Ab clearance.

Answer 20

Apoliporotein E

Question 21

True or False

Tau is a highly soluble protein involved in the stabilization of microtubules.

Abundant in neurons

Exists in multiple isoforms

Answer 21

True

Question 22

In Alzheimer’s, tau becomes _____________________. This causes tau to dissociate from microtubules and form assemblies of paired helical filaments. Dissociation of tau from microtubules causes loss of microtubule stability and promotes breakdown. This leads to neuronal dysfunction.

Answer 22

hyperphosphorylated

Question 23

What does the amyloid cascade hypothesis state?

Answer 23

That extracellular AB causes synaptic effects that alter intracellular phosphorylation of tau protein leading to microtubule breakdown.

Question 24

True or False

Alzheimer’s causes exaggerated degeneration of the temporal cortex and hippocampus combined with severe loss of cholinergic neurons that supply input to both.

Answer 24

True

Question 25

The cholinergic system is an ascending neuromodulatory system that uses acetylcholine as a neurotransmitter.

Output from it to cortex and hippocampus originate from the basal forebrain.

True or False

• Alterations of acetylcholine neurotransmission can lead to minor improvement for Alzheimer’s patients but have no effect on disease progression.

Answer 25

True

Question 26

True Or False

The hippocampus plays a critical role in the formation of new memories, which is severely impaired with Alzheimer’s.

• More advanced Alzheimer’s causes deficits in previously formed long-term memories. This is consistent with research suggesting distributed long-term memory storage across the cortex.

Answer 26

True

Question 27

___________is also sometimes called multi-infarct dementia because it causes widespread brain damage through a series of minor strokes, often not individually detectable.

_____________causes exaggerated neurodegeneration of frontal cortex compared to Alzheimer’s. This results in deficits in the executive function being most severe (e.g., think of Phineas Gage), with memory impairments coming later in FTD progression.

True or False

• FTD often involves aggregates of tau protein, but rarely involves amyloid-beta plaques.

Answer 27

• Vascular dementia

Frontal-temporal dementia (FTD)

true