CNS Protein Anomalies: Prions and Amyloids (Msq Drill 276)

1. New Guinea, Cannibalism of human brain, severe involvement of CEREBELLUM, extracellular plaques.

CJD

GSS

Kuru

2. When can the diagnosis of prion disease or alzheimer's disease be definitively made?

By MRI

At autopsy

After a mental status exam

By CT scan

3. Which of the prion proteins - Prpc or PrPsc forms multimeric aggregates and is protease resistant?

PrPsc

PrPc

4. Bovine spongiform encephalopathy is commonly known as:

Elephantisis

Mad cow disease

Scrapie

Transmissible mink encephalopathy

5. What is the leading cause of dementia?

Parkinson's disease

Alzheimers disease

CJD

6. Familial CJD is inherited in an __________ pattern.

Autosomal recessive

Autosomal dominant

X-linked recessive

X-linked dominant

7. PrPsc is more highly enriched in _______ . This leads to its aggregations and resistance within the cell.

Beta pleated sheets

Alpha helice sheets

8. Can cognitively intact elderly patients also exhibit senile plaques?

Yes

No

9. Between alzheimers disease and CJD which one is accompanied by muscle twitching and loss of coordination?

Alzheimers

CJD

10. Prion disease: mean age of onset was 26 y/o, longer duration of illness (12 months), sporadic cases. Exhibited more behavioral and sensory disturbances. No EEg findings.

What is the prion disease?

CJD

New variant CJD AKA mad cow disease

Alzheimers disease

Huntington's disease

11. Prion diseases are also referred to as:

Non-transmissible spongiform encephalopathies

Transmissible spongiform encephalopathies (TSE)

Ungulate spongiform encephalopathies

Chronic wasting diseases

12. Do protein conformational diseases involve proteins that were initially normal or that were already malformed?

Initially normal proteins

Initially abnormal proteins

13. The process of prion protein propagation is exponential and _____ .

Autocrine

Autocatalytic

Exocrine

Exocatalytic

14. Can prion proteins become infectious?

No

Yes

15. Hyperphosphorylation of tau leads to its aggregation. these are known as ______________ and are found in Alzheimers disease.

Cluster like lesions

Neurofibrillary tangles

Tau like entanglements

Tau inclusion bodies

16. Prion protein:

Prion disease

Alzheimers disease

Corticobasal degeneration

Frontotemporal dementia

ALS

17. What does amyloid "mistakenly" mean?

Starch like

Protein like

Zinc like

Amino acid like

18. What is the most common form of TSE in humans?

GSS

Alzheimers disease

Creutzfeldt-Jacob Disease

Fatal familial insomnia

Kuru

19. The primary feature of protein conformational diseases is that of a normal cellular protein that becomes __ and _ .

Misfolded

Aggregated

Denatured

Compartmentalized

Submit

20. Beta-sheets typically have this quality:

They are soluble

They are insoluble

They are flexible

They are easily denatured

21. The animal prion disease found in sheep and goats is known as:

Mad cow disease

Scrapie

Chronic wasting disease

Feline spongiform encephalopathy

22. What cholesterol drug also reduces the levels of beta-amyloid in the brain?

Simvastatin

Lipitor

Rovastatin

Nystantin

23. Both _ and _ involve dementia.

Alzheimers disease

GSS

CJD

Submit

24. What is derived from protein/APP (amyloid precursor protein) and forms plaques in the brain?

Beta- amyloid

Alpha helix

Beta-2-microgloblulin

25. The normal prion protein is constitutively expressed as a:

Cytoplasmic body

Membrane glycoprotein

Vacoule

Endosome

Plasmid

26. The proteins that undergo conformational changes all involve what highly enriched protein?

Alpha helix

B-pleated sheets

Beta-2-microglobulin

Beta-trace proteins

27. Which of the following are the four main human forms of Prion diseses?

Creutzfeldt-jakob disease (CJD)

Mad cow disease

Gerstmann-Straussler-Scheinker disease (GSS)

Fatal familial insomnia (FFI)

Kuru

Submit

28. In which pathway is the amyloid-B protein fragment derived from?

Amyloidogenic pathway

Non-amyloidogenic pathway

29. Is vacoulization seen intracellularly or extracellularly?

Intracellularly

Extracellulary

Amyloid like proteins depositions are seen both intra and extra cellularly.

Explanation

Amyloid like proteins depositions are seen both intra and extra cellularly.

30. Most genetic diseases of amyloid aggregates are inherited in what pattern?

Autosomal recessive

X-linked recessive

X-linked dominant

Autosomal dominant

31. When deposition of proteins occurs, a ________ protein arrangement is visible when stained with Congo Red dye.

Microtubular

Circular

Fibrillar

Whirlpool like

32. In Alzheimers disease the tau protein is:

Dephosphorylated

Hyperphosphorylated

Denatured

Hydrolyzed

33. Superoxide dismutase:

Amyotropic lateral sclerosis

Alzheimers disease

Lewy body dementia

Prion disease

34. Are infectious prions normally destroyed by sterilization?

Yes

No

Prion proteins are extremely heat resistant, chemical and radiation resistant as well.

Explanation

Prion proteins are extremely heat resistant, chemical and radiation resistant as well.

35. Which of the following is a characteristic feature seen with CJD?

Slow progressing dementia

Rapidly progressive dementia

No dementia

Diagnosis is by ruling out other possiblities and EEG. Death is usually within 12 months of onset. Median illness duration is 4 months.

Explanation

Diagnosis is by ruling out other possiblities and EEG. Death is usually within 12 months of onset. Median illness duration is 4 months.

36. Which of the prion diseases affects the cerebrum?

CJD

GSS

Parkinson's disease

37. Gerstmann-Straussler-Scheinker syndrome is a familial prion disease with AD inheritance. Which of the following is characteristic of this disease?

Dementia with no cerebellar involvement

Spinocerebellar ataxia with dementia

38. What histopathological finding is responsible for the spongiosis or spongiform degeneration of prion diseases?

Membrane glycoproteins

Vacoulized cells

Neurofibrillary tangles

Whirlpool like cell structure

39. B-Amyloid and tau are involved in the pathogenesis of Alzheimer's disease. Which of the two uses microtubules and is thus associated with intracellular accumulations?

B-amyloid

Tau

B-amyloid is primarily extracellular

Explanation

B-amyloid is primarily extracellular

40. Smaller _________ attach to the oligomers and a seeding of the amyloids occurs.

Dimers

Monomers

Trimeric aggregates

Amyloid aggregates

41. Presenilin is involved in:

APP processing

Amyloid deposition

Neurofibril formation

42. Which of the causes of CJD shows age related somatic mutations of the PRNO or spontaneous conversion of PrPc into PrPsc?

Iatrogenic CJD

Sporadic CJD

Familial CJD

43. The early phase of amyloid seeding is called the:

Log phase

Lag phase

Growth phase

Termination phaseh

44. The amyoloid precursor protein is a _____________ highly enriched in neuronal cells.

Cytoplasmic protein

Membrane glycoprotein

Extracellular protein

Nuclear protein

45. When the aggregates are forming they are known as:

Dimers

Clusters

Oligomers

46. Amyloid like proteins are generally in their ________ form before they form aggregates.

Dimeric

Trimeric

Aggregrate

Monomeric

47. Tau is a microtubule assoicated protein (MAP) that has what function?

To stabilize synaptic terminals

To stabilize neuronal microtubules

To facilitate neuronal transport

To facilitate endocytosis

48. CJD, Kuru and GSS all affect which part of the brain?

Cerebrum

Cerebellum

Cortex

Brainstem

Limbic system

49. Which of the following is an immunotherapy that is used to stimulate a patient's immune system in order to target and degrade beta amyloid?

Pro-B amyloid vaccination

Anti-B amyloid vaccines

Pro-APP vaccination

Anti-APP vaccination

50. Which of the following are neuropathological manifestions of Alzheimer's disease. Check all that apply.

Extracellular amyloid plaques

Extracellular neurofibrillary tangles from tau accumulation

Intracellular neurofibrillary tangles from tau accumulation

Intracellular amylod plaques

Submit

51. Cell death in prion diseases is by apoptosis, therefore this is evidence that there is :

No inflammation

Cell to cell damage

Massive infiltrative amounts of neutrophils

Necrosis

52. Prions acquired though contaminated EEG electrodes or neurosurgical instruments, corneal transplants, dura mater grafts, human pituitary derived human growth hormone.This is classified as _______ .

Infectious CJD

Infectious GSS

Iatrogenic CJD

Most cases have been eliminated through proper decontamination or autoclave and screening guidelines.

Explanation

Most cases have been eliminated through proper decontamination or autoclave and screening guidelines.

53. The pathogenic form or prion protein is known as PrPsc -. Is the amino acid sequence of this pathogenic form different from the normal form?

Yes

No

They both have the same amino acid sequence.

Explanation

They both have the same amino acid sequence.

54. The PrPsc monomers that are fomred are unstable, as a result they ________ in order to become stable.

Mutate

Change their conformation

Self propagate

Denature themselves

55. Which of the following are the three clinical halmarks of prion diseases? check all that apply.

Psychiatric features

Dementia

Ataxia

Depression

Myoclonus

ataxia is loss of muscle coordination. myoclonus is involuntary muscle twitching.

Explanation

ataxia is loss of muscle coordination. myoclonus is involuntary muscle twitching.

Submit

56. Tarenflubril/R-flubiprofen are _________ used to reduce the formation of B-amyloid.

Alpha secretase inhibitors

Amyloidase inhibitors

Gamma-secretase inhibitors

Beta-secretase inhibitors

57. The amyloidogenic pathway requires what two enzymes? Check all that apply:

Alpha-secretase

B-secretase

Amyloidase

Gamma-secretase

Submit

58. What is the predominant pathway that process APP? (amyloid precursor protein)

Amyloidogenic pathway

Non-amyloid pathway

Precursory pathway

Glycosylation

59. The change in conformations that proteins undergo in protein conformational diseases include which of the following: Check all that apply:

Protein aggregations

Resistance to degradation

Abnormal accumulations

Protein denaturation

Cell toxicity

Submit

60. Match the disease with the protein in the next 6 questions:

tau protein: Check all that apply

Alzheimers

Parkinson's disease

Amyotropic lateral sclerosis

Pick's disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia

Submit

61. The human prion gene is located on chromosome

18

20

17

11

5

62. **** What are the hallmark pathological lesions of Alzheimer's disease? Chek all that apply.

Depositions

Plaques

Hypercellularity

Tangles

Pleomorphic cells

Submit

63. The prion proteins primarily follow:

Blood circulation

Lymphatic circulation

CSF circulation

64. What is the average age of onset of CJD?

20-25 years

55-75 years

40-50 years

60-70 years

several forms: heredity, sporadic, acquired

Explanation

several forms: heredity, sporadic, acquired

65. Amyloidosis are deposited:

In the blood stream

In the PNS

In an organ

In the CNS

Eg Alzheimers beta-amyloid deposition. Amyloid or amyloid-like proteins may be deposited systematically.

Explanation

Eg Alzheimers beta-amyloid deposition. Amyloid or amyloid-like proteins may be deposited systematically.

66. What makes Fatal Familial Insomnia profoundly different from the other prion disease? Check all that apply.

No dementia

Involvement of the thalamus

Extreme agitation

Profound diturbances in the sleep cycle

Submit

67. Which of the following are characteristics of prion diseases? Check all that apply.

Always inherited

Rapidly progressive

Fatal neurodegenerative disorders

Never inherited

Long incubation periods

Submit

68. When do you typically start to see symptoms of amyloid deposition diseases?

As soon as conformational changes occur

When the fibrillar deposits are visible

As soon as aggregation commenses

When 70% deposition has taken place

69. What are the three forms of prion diseases?

Acute

Infectious

Inherited

Subacute

Spontaneous

Submit

70. Amyloid proteins refers to any number of proteins that are deposited in cells and share selected ___________ features.

Conformational

Histologic

Symptomatologic

Laboratory

71. Do conformational diseases ALWAYS involve the deposition of altered protein?

Yes

No

72. Which of the following are arguments that have been posed in favor of protein aggregation being the cause of effects of the diseases that are manifested. Check all that apply.

Overexpression or mutated forms of the protein causing disease

New and emerging illnessess

Genetic associations

Co-localization of protein with cell loss

Submit

73. Alpha-synuclein: Check all that apply.

Prion disease

Parkinson's disease

Huntington's disease

Lewy body dementia

Submit

74. So if the pathogenic form of the prion protein has a similar amino acid sequence from the normal type, why is it disease causing? Check all that apply.

It becomes mutated in situ

It has a different conformation

It takes over the machinery of the nucleus

It has different patterns of glycosylation

this is what leads to its aggregation in the cell

Explanation

this is what leads to its aggregation in the cell

Submit

75. The PrPc or normal prion protein is primarily: Check all that apply.

Alpha-helical

Protease susceptible

A stable monomer

Monomeric species

Self propagating

the pthogenic forms PrPsc self propagates in order to change the normal form into the abnormal form. The mechanism is poorly understood.

Explanation

the pthogenic forms PrPsc self propagates in order to change the normal form into the abnormal form. The mechanism is poorly understood.

Submit

76. In which of the following conditions is there a genetic link between APP (amyloid precursor protein) and alzheimers disease? Check all that apply.

Trisomy 21

Presenilin gene mutations

Early onset Alzheirmers disease

Late onset Alzheimers disease

Familial Alzheimers disease

Submit

77. Which of the following are known routes of transmission of prion proteins?

Ingestion - GI, Mcells,Peyers,lymphoreticullar system, PNS, vagus or spinal cord, brain

Iatrogenic

Droplet transmission

Contaminated soil

Blood transfusions

Submit

CNS Protein Anomalies: Prions and Amyloids (Msq Drill 276)

1. New Guinea, Cannibalism of human brain, severe involvement of CEREBELLUM, extracellular plaques.

2.

What first name or nickname would you like us to use?

2. When can the diagnosis of prion disease or alzheimer's disease be definitively made?

3. Which of the prion proteins - Prpc or PrPsc forms multimeric aggregates and is protease resistant?

4. Bovine spongiform encephalopathy is commonly known as:

5. What is the leading cause of dementia?

6. Familial CJD is inherited in an __________ pattern.

7. PrPsc is more highly enriched in _______ . This leads to its aggregations and resistance within the cell.

8. Can cognitively intact elderly patients also exhibit senile plaques?

9. Between alzheimers disease and CJD which one is accompanied by muscle twitching and loss of coordination?

10. Prion disease: mean age of onset was 26 y/o, longer duration of illness (12 months), sporadic cases. Exhibited more behavioral and sensory disturbances. No EEg findings.What is the prion disease?

11. Prion diseases are also referred to as:

12. Do protein conformational diseases involve proteins that were initially normal or that were already malformed?

13. The process of prion protein propagation is exponential and _____ .

14. Can prion proteins become infectious?

15. Hyperphosphorylation of tau leads to its aggregation. these are known as ______________ and are found in Alzheimers disease.

16. Prion protein:

17. What does amyloid "mistakenly" mean?

18. What is the most common form of TSE in humans?

19. The primary feature of protein conformational diseases is that of a normal cellular protein that becomes ________ and _______ .

20. Beta-sheets typically have this quality:

21. The animal prion disease found in sheep and goats is known as:

22. What cholesterol drug also reduces the levels of beta-amyloid in the brain?

23. Both _____ and _____ involve dementia.

24. What is derived from protein/APP (amyloid precursor protein) and forms plaques in the brain?

25. The normal prion protein is constitutively expressed as a:

26. The proteins that undergo conformational changes all involve what highly enriched protein?

27. Which of the following are the four main human forms of Prion diseses?

28. In which pathway is the amyloid-B protein fragment derived from?

29. Is vacoulization seen intracellularly or extracellularly?

30. Most genetic diseases of amyloid aggregates are inherited in what pattern?

31. When deposition of proteins occurs, a ________ protein arrangement is visible when stained with Congo Red dye.

32. In Alzheimers disease the tau protein is:

33. Superoxide dismutase:

34. Are infectious prions normally destroyed by sterilization?

35. Which of the following is a characteristic feature seen with CJD?

36. Which of the prion diseases affects the cerebrum?

37. Gerstmann-Straussler-Scheinker syndrome is a familial prion disease with AD inheritance. Which of the following is characteristic of this disease?

38. What histopathological finding is responsible for the spongiosis or spongiform degeneration of prion diseases?

39. B-Amyloid and tau are involved in the pathogenesis of Alzheimer's disease. Which of the two uses microtubules and is thus associated with intracellular accumulations?

40. Smaller _________ attach to the oligomers and a seeding of the amyloids occurs.

41. Presenilin is involved in:

42. Which of the causes of CJD shows age related somatic mutations of the PRNO or spontaneous conversion of PrPc into PrPsc?

43. The early phase of amyloid seeding is called the:

44. The amyoloid precursor protein is a _____________ highly enriched in neuronal cells.

45. When the aggregates are forming they are known as:

46. Amyloid like proteins are generally in their ________ form before they form aggregates.

47. Tau is a microtubule assoicated protein (MAP) that has what function?

48. CJD, Kuru and GSS all affect which part of the brain?

49. Which of the following is an immunotherapy that is used to stimulate a patient's immune system in order to target and degrade beta amyloid?

50. Which of the following are neuropathological manifestions of Alzheimer's disease. Check all that apply.

51. Cell death in prion diseases is by apoptosis, therefore this is evidence that there is :

52. Prions acquired though contaminated EEG electrodes or neurosurgical instruments, corneal transplants, dura mater grafts, human pituitary derived human growth hormone.This is classified as _______ .

53. The pathogenic form or prion protein is known as PrPsc -. Is the amino acid sequence of this pathogenic form different from the normal form?

54. The PrPsc monomers that are fomred are unstable, as a result they ________ in order to become stable.

55. Which of the following are the three clinical halmarks of prion diseases? check all that apply.

56. Tarenflubril/R-flubiprofen are _________ used to reduce the formation of B-amyloid.

57. The amyloidogenic pathway requires what two enzymes? Check all that apply:

58. What is the predominant pathway that process APP? (amyloid precursor protein)

59. The change in conformations that proteins undergo in protein conformational diseases include which of the following: Check all that apply:

60. Match the disease with the protein in the next 6 questions:tau protein: Check all that apply

61. The human prion gene is located on chromosome

62. **** What are the hallmark pathological lesions of Alzheimer's disease? Chek all that apply.

63. The prion proteins primarily follow:

64. What is the average age of onset of CJD?

65. Amyloidosis are deposited:

66. What makes Fatal Familial Insomnia profoundly different from the other prion disease? Check all that apply.

67. Which of the following are characteristics of prion diseases? Check all that apply.

68. When do you typically start to see symptoms of amyloid deposition diseases?

69. What are the three forms of prion diseases?

70. Amyloid proteins refers to any number of proteins that are deposited in cells and share selected ___________ features.

71. Do conformational diseases ALWAYS involve the deposition of altered protein?

72. Which of the following are arguments that have been posed in favor of protein aggregation being the cause of effects of the diseases that are manifested. Check all that apply.

73. Alpha-synuclein: Check all that apply.

74. So if the pathogenic form of the prion protein has a similar amino acid sequence from the normal type, why is it disease causing? Check all that apply.

75. The PrPc or normal prion protein is primarily: Check all that apply.

76. In which of the following conditions is there a genetic link between APP (amyloid precursor protein) and alzheimers disease? Check all that apply.

77. Which of the following are known routes of transmission of prion proteins?

10. Prion disease: mean age of onset was 26 y/o, longer duration of illness (12 months), sporadic cases. Exhibited more behavioral and sensory disturbances. No EEg findings.

What is the prion disease?

19. The primary feature of protein conformational diseases is that of a normal cellular protein that becomes __ and _ .

23. Both _ and _ involve dementia.

60. Match the disease with the protein in the next 6 questions:

tau protein: Check all that apply