Genetics of Alzheimers disease and treatments

Question 1

what causes Alzheimers disease

Answer 1

1. chromosomal- trisomy 21 (downs syndrome)
2. familial (strong genetic component)
   - early onset familial
   - late onset familial
3. idiopathic (non familial)
   - includes gene/environment interactions

Question 2

what is apolipoprotein E

Answer 2

1. metabolises fats in the body
2. interacts significantly with low density lipoprotein receptors
3. produced by astrocytes in the CNS and is the principle cholesterol carrier to neurons via APOE receptors
4. 3 major alleles: APOE2 ,3 and 4

Question 3

what is the compliment receptor 1

Answer 3

1. encoded by the CR1 gene on chromosome 1
2. CR1 protein mediates cellular binding to immune complexes and antibodies on erythrocytes, leukocytes etc
3. a negative regulator of the complement cascade, mediate immune adherence and phagocytosis and inhibit both the classic and alternative pathways
4. certain alleles are a risk factor in the development of late onset AD

Question 4

What are triggering receptor expressed on myeloid cells-2 (TREM2)

Answer 4

1. encoded by the TREM2 gene on chromosome 6
2. plays and important anti inflammatory role in the brain
3. homozygous mutations in TREM2 increases risk of AD, Parkinson’s disease and amyotrophic lateral sclerosis
4. mutation R47H confers a significant risk of AD

Question 5

What inhibitors are involved in the treatment of alzhiemers disease

Answer 5

1. cholinesterase inhibitors
2. NMDA uncompetitive antagonists
3. B-amyloid and tau
4. aducanumab
5. secretase inhibitors