Neurodegeneration and Neurodegenerative Diseases

Question 1

Neurodegeneration

Answer 1

Progressive loss (death) of neurons beyond that of the normal aging process.
It is a problem because neurons cannot be replaced.

Question 2

What is the most important risk factor for the common neurodegenerative diseases?

Answer 2

Age

Question 3

Causes of neurodegeneration

Answer 3

• Neurodegenerative diseases
• Cancer
• Trauma (head/spine injury)
• Viral diseases/Infections
• Vascular/Circulatory disorders.
• Developmental disorders

Question 4

Examples of vascular and circulatory disorders that can cause neurodegeneration

Answer 4

Strokes
Narrowing of blood vessels (atherosclerosis)
Thrombosis
etc.

Question 5

Venous infarction

Answer 5

Usually results from venous sinus thrombosis
Risk factors include states that result in hyperviscosity or increased coagulability
Generally they are very hemorrhagic

Question 6

Flow gradient

Answer 6

Heterogenous regional blood flow (CBF) reduction after focal ischemia

Question 7

Densely ischemia

Answer 7

Region surrounded by areas of less severe CBF reduction

Question 8

Ischemic penumbra

Answer 8

An area of reduced perfusion sufficient to cause potentially reversible clinical deficits but insufficient to cause disrupted ionic homeostasis

Question 9

Pathophysiology of ischemic brain injury

Answer 9

At the start the area of penumbra is large, but as time goes by without treatment this becomes infarction

Question 10

Infections that can cause Neurodegeneration

Answer 10

• Meningitis – infection of the blood vessel membrane of the brain
• Cerebral abscess
• Subdural empyema
• Viral encephalitis
• Cerebritis

Question 11

What do dementive diseases cause?

Answer 11

The loss of mental faculties

Question 12

What makes dementive diseases special?

Answer 12

Often the cause is unknown
No cure
Progressive and irreversible

Question 13

Types of neurodegenerative diseases

Answer 13

Dementia
Movement disorders
Motor neuron disease (ALS)

Question 14

Dementia

Answer 14

Alzheimer’s disease: common, amyloid hypothesis, plaques and tangles, gross brain atrophy
Prion disease: rare, “transmissible” protein, rapidly progressive, vacuolar changes

Question 15

Movement disorders

Answer 15

Parkinson’s disease: hypokinetic, loss of dopaminergic cells substantia nigra, Lewy bodies
Huntington’s disease: choreiform movements, caudate atrophy, nuclear inclusions

Question 16

Motor Neuron Disease (ALS)

Answer 16

Loss of upper and lower motor neurons, progressive over 2-5 years

Question 17

Time Course for a ND patient

Answer 17

Develop minor psychological/behavioural or motor issues (50 years)
Begin differential diagnosis (may take a year)
Early treatment aimed at quality of life/diet/exercise
Treatments to delay symptoms (Years)
Treatments to alleviate worsening symptoms (Years)
Patient’s symptoms become severe (palliative care)
Patient dies from secondary disease eg pneumonia

Question 18

Polio

Answer 18

Poliomyelitus is caused by an RNA virus, the poliovirus
Enters the CNS in 3% of cases and in 1% leads to focal loss of motoneurons in the spinal cord.

Question 19

Rostra-caudal/medio-lateral topographical map

Answer 19

Study of spinal motoneuron loss in polio and comparison to the resulting loss of muscle control allowed mapping of motoneuron foci in the spinal cord to the innervated muscle

Question 20

Amyloidogenic diseases

Answer 20

Neurodegenerative diseases where there is deposition of an abnormal protein isoform.
These aggregates can be inside or outside of the cell
E.g: Alzheimer’s, Parkinson’s, Prion diseases

Question 21

Prion diseases

Answer 21

Very rare
Experimentally transmissible
Human and animal diseases are fairly similar, so animal models are useful.
Generally due to mutations in the prion protein

Question 22

Characteristics of prion diseases

Answer 22

• Long incubation period of infection (10-40 years)
• Deposition of large amounts of abnormal prion protein
• Rapid neuronal loss
• Gliosis
• Vacuoles
• Short symptomatic period (6-18 months)

Question 23

Metal hypothesis

Answer 23

AD, PD and Prion disease are all linked to a protein that occurs normally in the brain
In each case the protein binds copper.
In each case there is a suggestion that metals play some role in the cause (either iron or copper).

Question 24

Demyelinating diseases

Answer 24

Acquired disorders of myelin, such as multiple sclerosis

Question 25

Dismyelinating diseases

Answer 25

Genetic disorders of myelin and its turnover, such as leukodystrophies

Question 26

Possible causes of ND

Answer 26

Aggregates - toxicity
Inflammation - microglia going wrong
Oxidative stress - tau
Mitochondrial damage