Neurodegeneration Flashcards
Importance of researching dementia (stats and science)
A third of people born will get dementia
In 2010, 35 million people with dementia which is predicted to double every 20 years so in 2040 will be only second to cancer for the cause of morbidity in the first world
Range of diseases with different pathologies and causes
Losing different types of neurons at different stages that require different drugs to target
Currently no drug therapies that will stop or slow progression of disease
Types of dementia, cause, characteristics
Dementia is a neurodegenerative disease that covers multiple diseases. Each has their associated protein that’s initially lost in disease onset
Alzheimer’s Disease (amyloid precursor protein; APP and microfilament protein Tau associated with misfolding and aggregation)
Frontotemporal dementia/Picks disease (Tau, MAPT gene)
Parkinson’s Disease (alpha synuclein)
Dementia with Lewy Bodies (alpha synuclein)
Huntington’s Disease (Huntingtin protein; more copies of glutamate repeats has worse symptoms)
Vascular Dementia (for those in which little is understood in animals)
Creutzfeldt-Jakob disease (Prion protein)
Amyloidosis: All have misfolded proteins aggregating into amyloid-like structures (prion-like) and spread like an infection (in ways we don’t understand) but pathology is probably associated with misfolding of amyloid proteins
Acetylcholine: Cholinergic hypothesis in AD, method of activating,
In Alzheimer’s there’s a loss of degeneration of cholinergic neurons in the basal forebrain and the associated loss of cholinergic neurotransmission in the cerebral cortex and other areas contributed significantly to the deterioration in cognitive function (memory loss, etc) seen in patients
Acetylcholine release from the presynaptic neuron to postsynaptic neuron activates one of 5 subtypes of muscarinic receptors
Important in any signalling to be able to stop signal to control signal transduction
Acetylcholine after signal quickly gets degraded by acetylcholinesterase
Studies investigated to improve earlier identification of Alzheimer’s
Genome wide association studies to attempt to identify gene associated with Alzheimer’s
Hard to identify a genetic predisposition
Still understanding genetic and environmental contributions
Current Frontline treatment of MCI in AD
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal
Emesis
Amyloid Hypothesis
- Familial AD (FAD) is caused by autosomal dominant mutations in either APP, on chromosome 21, or the presenilin (PS1, PS2) genes on chromosomes 14 and 1 respectively.
- Sporadic idiopathic late on-set risk factor the apolipoprotein (Apo) E4 allele on chromosome 19
