Neurodegeneration

Question 1

Main types of neurodegenerative disorders:

Answer 1

• taupathies
• amyloidopathies
• alpha-synucleinopathies (intracellular protein aggregates)
• TDP-43 proteinopathies (intracellular protein aggregates)
• polyglutaminopathies (intracellular protein aggregates)
  etc. etc.

Question 2

Taupathies:

Answer 2

Alzheimer's disease 
Progressive Supranuclear Palsy
Corticobasal degeneration
Parkinson-demential/ALS complex
Frontotemporal dementia with Parkinsonism
Argyrophilic grain disease 
Pallido-ponto-negral degeneration
Sporadic Multiple system atrophy with degeneration

Question 3

Amyloidopathies

Answer 3

Alzheimer’s
Down syndrome
Hereditary cerebral hemorrhage with amyloidosis

Question 4

alpha-Synucleinopathies

Answer 4

Parkinson disease
Multiple system atrophy
Hallervorden-Spatz disease

Question 5

TDP-43 proteinopathies

Answer 5

Frontotemporal lobe dementia
ALS
Dementia with Lewy bodies
PERRY syndrome

Question 6

Polyglutamine repeat disorders (Polyglutaminopathies)

Answer 6

Huntington's, rigid type
Choreoacanthocytosis (neuroacanthocytosis)
Spinocerebellar ataxias (SCA), hereditary
Friedreich ataxia (FRDA)
Machado–Joseph disease
Kennedy disease (spinobulbar nuclear atrophy)
Dentatorubropallidoluysian atrophy (DRLPA)

Question 7

Worldwide human allele frequencies of ApoE

Answer 7

• E4/E4 - 2% (15x higher chance with AD than E3/E3)
• E3/E3 - 60%
• E2/E4 + E3/E4 - 30% (when 1 allele of E4 is present: 3-4x higher chance of AD)
• E2/E3 - ?<8%

Question 8

Braak Stages I & II

Answer 8

I - cortex involvement confined to the transentorhinal region

II - more neurofibrillary tangles in the transentorhinal region

• modest involvement of CA1
• virtual absence of isocortical changes

Question 9

Braak Stages III & IV

Answer 9

III - severe involvement of layer Pre-a, both in transentorhinal and entorhinal regions.
- first ghost tangles become visible in transentorhinal layer

IV - large numbers of ghost tangles in both of the above regions.

- numerous NFTs in CA1
- mild involvement of the subiculum
- almost to changes to the isocortex and primary sensory and motor areas

Question 10

Braak stages V & VI

Answer 10

V - involvement of all components of the hippocampal formation

VI - extensive neocortical involvement
- NFT bearing granule cells in the fascia dentata