Neuro 1

Question 1

What are NDDs?

Name a few

Answer 1

Gradually progressive death of neurones in the central nervous system …

– dominantly inherited conditions e.g. Huntington’s are sometimes included

– core NDDs Alzheimer’s, Parkinson’s, dementia with Lewy bodies, motor neurone disease

Question 2

Outline the fundamental pathology of these “core” NDDs

Answer 2

– a normal protein takes on an abnormal form – misfolding, hyper-phosphorylation
– this aggregates into oligomers and later into visible inclusion bodies
– the protein’s normal function is lost; oligomers are toxic (inclusions too?)
– the neurone loses function, then dies, then disappears

Question 3

Describe the pathogenesis of Alzheimers

Answer 3

– tau normally stabilises microtubules; aggregates in Alzheimer’s

• neuronal inclusions: neurofibrillary tangles, containing tau protein
• beta-amyloid, containing Aβ protein - extracellular (unusual!)
• amyloid also often in walls of arterioles ‘cerebral amyloid angiopathy’

Amyloid appears first, tau location correlates with cognitive deficits
=> probably amyloid doesn’t damage neurones but triggers tau which does
Often co-exists with small-vessel cerebrovascular disease – this worsens cognitive deficits
May also co-exist with Lewy body pathology

Question 4

Describe the pathogenesis of PD

Answer 4

alpha-synuclein found throughout neurones, unclear function; aggregates in Parkinson’s

Question 5

Describe the pathogenesis of MND

Answer 5

TDP-43 nuclear protein, binds DNA and RNA; aggregates in MND

Question 6

What are the risk factors for AD?

Answer 6

• One common genetic polymorphism: apolipoprotein E (ApoE, three alleles, ε4 highest risk)
• Rare dominantly inherited single genes: PSEN1, PSEN2, APP (onset in early-mid adulthood)
• Some residual genetic risk, presumably many interacting loci each with small effect
• Cognitive reserve: stronger cognitive function pre-morbidly => later diagnosis
• Vascular risk factors: CVD worsens AlzD symptoms, but does it hasten AlzD pathology?

Question 7

Some treatments for AD

Answer 7

AChE inhibitors and memantine boost cognitive function

Question 8

What is Parkinson’s Disease?

Answer 8

Region: Substantia nigra
Cell type: Dopaminergic nigrostriatal neurone
Pathology: Neuronal loss, Lewy Bodies

Question 9

What is ALD (MND)? Amyotrophic Lateral Sclerosis

Answer 9

• Region: Primary motor cortex
  - Highly selective
  processes
• Cell type: Layer 5 pyramidal neurons
• Pathology: Neuronal loss, TDP-43 inclusions

Question 10

What are the findings on FDG-PET scan?

Answer 10

Common finding in Alzheimer’s is cold spots in parietal lobe (sparing frontooccipital lobes)

• taking up less glucose