Alzheimer's disease
Alzheimer's disease is a progressive degenerative disease of the brain accounting for the majority of dementia seen in the UK
Genetics
Pathological changes
Neurofibrillary tangles
Management
Genetics
- most cases are sporadic
- 5% of cases are inherited as an autosomal dominant trait
- mutations in the amyloid precursor protein (chromosome 21), presenilin 1 (chromosome 14) and presenilin 2 (chromosome 1) genes are thought to cause the inherited form
- apoprotein E allele E4 - encodes a cholesterol transport protein
Pathological changes
- macroscopic: widespread cerebral atrophy, particularly involving the cortex and hippocampus
- microscopic: cortical plaques due to deposition of type A-Beta-amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein
- biochemical: there is a deficit of acetylecholine from damage to an ascending forebrain projection
Neurofibrillary tangles
- paired helical filaments are partly made from a protein called tau
- in AD are tau proteins are excessively phosphorylated
Management
- NICE now recommend the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer's disease
- memantine (a NMDA receptor antagonist) is reserved for patients with moderate - severe Alzheimer's