Genetics of Neurodegeneration (Dementia)

Question 1

What is Dementia

Answer 1

General term for a group of neurological conditions that cause a decline in cognitive function

Question 2

Symptoms of Dementia

Answer 2

Question 3

Familial Alzheimer’s Disease

Answer 3

Caused by missense mutations in PSEN1 (Chromosome 14) and PSEN2(Chromosome 1)

Question 4

Dementia with Lewy bodies

Answer 4

Caused by mutation in a-Synuclein gene

Question 5

Frontal Temporal Dementia

Answer 5

Can be caused in single gene mutations e.g C9ORF72, TDP-43, FTDP-17

Question 6

Apolipoprotein E (APOE)

Answer 6

• APOE gene on Chromosome 19 codes for Apolipoprotein E (Protein involved in lipid trafficking)
• APOE is present in human populations as a number of different alleles (e2, e3, e4), differentiated by coding
  variation

Question 7

TREM2

Answer 7

• Located on Chromosome 6 encodes a receptor protein found on immune cells, including microglial cells in the central nervous system
• Coding mutations in TREM2 cause a
  rare autosomal recessive form of
  dementia (Nasu-Hakola disease)
• Heterozygous coding variants
  increase risk of developing Alzheimer’s disease

Question 8

Amyloid Cascade Theory

Answer 8

Suggests that Alzheimer’s is caused by a build up of Amyloid-B in brain

Question 9

Modifying the course of Alzheimer’s disease

Answer 9

Question 10

Drug Development Efforts

Answer 10

• Identifying and understanding genome wide associated genes

-Bridging the gap between Mendelian forms and idiopathic disease

• Integrating genetics, imaging and biomarkers to identify those most at risk

-Understand the temporal staging of amyloid deposition, tau accumulation, inflammatory response and neuronal loss