Neurodegenerative Diseases Flashcards
(43 cards)
Define neurogeneration
Progressive loss of neurons
Define Neurodegenerative disease
Any disease caused by neurodegeneration
What are some patterns with neurogenerative diseases based on the age of onset?
Earlier age of onset = greater genetic contribution
Later age of onset = more likely a sporadic
What are the characteristics of neurodegenerative diseases?
Highly heterogenous
- some disease names are really umbrella terms
- some diseases are inherently pleiotropic
What are the common features of neurodegenration?
- Molecular impairment somewhere in the cell
- Decreased transmission at synapse
- “Dying back” of neurites (axons or dendrites)
- Cell death
What is defined as a neurones “Achilles heal”?
Distance between the axon terminal and nucleus
What do neurodegenerative diseases frequently involve?
Protein aggregation
Lysosomal dysfunction
Mitochondrial dysfunction
Associated inflammation via activation of Glia
Why is it hard to treat and research neurodegenerative diseases?
They rarely manifest overt signs and symptoms until long after neurodegeneration has begun
- early treatment is impossible without early diagnosis
- therapeutic challenge is considerable
Studies of affected tire is very difficult until death
Remain incurable
What is Alzheimer’s?
Most common neurodegenerative disease and most common cause of dementia
Onset usually >65
What is dementia?
A decline in memory and other cognitive function that impair quality of life.
Eg. Lost in own neighbourhood or recognise faces of family members
NOT NORMAL AGEING
What are the pathological hallmarks of Alzheimer’s?
Brain shrinkage
Proteinopathies
- amyloid plaques
(Extracellular protein aggregates)
(Enriched in A-beta peptides) - neurofibrillary tangles /helical filaments
(Intracellular protein aggregates)
(Enriched in Tau protein)
What is A-beta?
Peptide cleaved from a transmembrane protein called amyloid beta precursor protein (APP) by proteases
What mutation involved in A-beta peptide processing are thought to cause rare early onset forms of Alzheimer’s?
APP gene
PSEN 1 gene - presenile 1
PSEN2 gene - presenile 2
What is tau?
A protien that normally binds to axons in microtubules
What is the function of tau?
Hyperphosphorylated and becomes displaced
- forms tangles
- forms destabilised microtubules (as it detaches)
What are the 3 main roles of microtubules in post-mitotic cells?
- structure/shape of cell
- positioning of organelles
- motorways for transporting vesicular cargo
In typical late onset Alzheimer’s disease what is observed?
- neurofibrillary tangles are seen before amyloid plaques
- neurofibrillary tangles are well correlated with cell death and progression
What is the Tau hypothesis?
Suggests Tau is upstream A-Beta
Why are scientists debating weather amyloid or Tau have a bigger contribution to Alzheimer’s?
- more evidence for amyloid HOWEVER therapies inhibiting A beta aggregation haven’t worked
So far - tangles and plaques may be red herrings (could be pathogenic, or by standers or even protective)
What are risk factors of developing Alzheimer’s?
Down syndrome (APP on chromosome 21)
Gender (more in women)
High BP, cardiovascular disease, diabetes
Low education
Head injury
Smoking and drinking
- only a small genetic risk condition for late onset
What is Parkinson’s disease?
Second most common neurodegenerative disease
A movement disorder
Usually 60-65 years
What are the motor symptoms of Parkinson’s?
- resting Tremor (trembling hands and feet)
- Bradykinesia (slow movement)
- Rigidity
- postural instability (fall over)
What are the non motor symptoms of Parkinson’s disease?
Depression + Anxiety
Loss of smell
Sleep disorders
Constipation
Dementic
What are the pathological hallmarks of Parkinson’s?
Loss of dopaminergic neurons of the substantial nigra (part of basal ganglia in midbrain).
Proteinopathy - Lewy bodies
Intracellular protein aggregates
Enriched in a synuclein protein
