L18 - Neurodegeneration

Question 1

What are neurodegenerative disease?

Answer 1

Disorders characterised by progressive degeneration or loss of neurons, leading to cognitive, motor and functional impairments

Question 2

What are some common neurodegenerative diseases

Answer 2

Alzheimer’s Disease (AD)

Parkinson’s Disease (PD)

Huntington’s Disease (HD)

Multiple Sclerosis (MS)

Amyotrophic Lateral Sclerosis (ALS)

Question 3

What are transmissible spongiform encephalopathies (TSEs)?

Answer 3

Fatal brain disease caused by prions, such as Creutzfeldt-Jakob Disease (CJD) and Bovine Spongiform Encephalopathy (BSE or mad cow disease).

Question 4

How do prions cause disease?

Answer 4

Prions are infectious proteins that replicate by converting normal cellular proteins into abnormally folded copies, leading to brain damage.

Question 5

What are symptoms of Creutzfeldt-Jakob Disease (CJD)?

Answer 5

Personality changes

memory loss

impaired thinking

insomnia

jerky movements

rapid mental deterioration.

Question 6

What are the 4 major human prion diseases?

Answer 6

Creutzfeldt-Jakob Disease, Gerstmann-Sträussler-Scheinker Syndrome, Fatal Familial Insomnia, and Kuru.

Question 7

What are the main phases of Alzheimer’s Disease (AD)?

Answer 7

Preclinical AD: Abnormal biomarkers, no symptoms.

Mild Cognitive Impairment (MCI): Cognitive decline without impaired daily living.

Dementia: Progressive loss of cognitive and functional abilities.

Question 8

What are the histopathological hallmarks of Alzheimer’s Disease?

Answer 8

Extracellular amyloid-beta plaques and intracellular tau tangles.

Question 9

What imaging techniques are used to diagnose Alzheimer’s Disease?

Answer 9

CT, MRI, PET scans, and FDG PET to detect energy use abnormalities.

Question 10

What biomarkers are analyzed in Alzheimer’s Disease?

Answer 10

Cerebrospinal fluid (CSF) levels of amyloid-beta 42 and phosphorylated tau.

Question 11

What is the amyloid hypothesis?

Answer 11

Alzheimer’s is driven by the accumulation of amyloid-beta plaques that disrupt neuronal function.

Question 12

What is the tau hypothesis?

Answer 12

Alzheimer’s progression is linked to the spread of tau protein tangles.

Question 13

What are the stages of tau tangle progression?

Answer 13

Stages I-II: Entorhinal cortex and locus coeruleus.

Stages III-IV: Hippocampus and parts of the neocortex.

Stages V-VI: Extensive spread throughout the neocortex.

Question 14

Name some amyloid-reducing drugs and their effects.

Answer 14

Aducanumab: FDA-approved, reduces amyloid-beta plaques but with uncertain clinical benefits.

Donanemab: Slows cognitive decline by 30–35%.

Lecanemab: Slows cognitive decline by 27%.

Question 15

What are common side effects of amyloid-reducing drugs?

Answer 15

Brain swelling, small bleeding, headache, dizziness, and nausea.

Question 16

What causes Parkinson’s Disease?

Answer 16

Degeneration of dopamine-secreting neurons in the substantia nigra, affecting the nigrostriatal pathway.

Question 17

What are the core motor symptoms of Parkinson’s Disease?

Answer 17

Tremor, bradykinesia (slowness of movement), and rigidity.

Question 18

What behavioral symptoms are associated with Parkinson’s Disease?

Answer 18

Anxiety, depression, sleep disorders (e.g., REM sleep behaviour disorder), and mood changes.

Question 19

What is the pathological hallmark of Parkinson’s Disease?

Answer 19

Lewy bodies containing the protein alpha-synuclein

Question 20

How does dopamine replacement therapy help Parkinson’s patients?

Answer 20

It alleviates motor symptoms by supplementing dopamine levels.

Question 21

What is the “prion paradigm” in neurodegenerative diseases?

Answer 21

Misfolded proteins like amyloid-beta, tau, and alpha-synuclein propagate neurodegeneration through aggregation and spread.

Question 22

How does neurodegeneration progress in Alzheimer’s Disease?

Answer 22

Tau tangles spread from the entorhinal cortex to the hippocampus and eventually to the neocortex.

Question 23

How does neurodegeneration progress in Parkinson’s Disease?

Answer 23

Alpha-synuclein spreads from the substantia nigra to other brain regions, causing motor and cognitive dysfunction.

Question 24

Why is early diagnosis of neurodegenerative diseases important?

Answer 24

Early intervention can slow progression and improve quality of life.

Question 25

What are the challenges in treating neurodegenerative diseases?

Answer 25

Treatments often alleviate symptoms but do not halt or reverse disease progression.

Question 26

What is the significance of biomarkers in neurodegenerative diseases?

Answer 26

They help in early detection, monitoring progression, and evaluating treatment efficacy.