Class notes

NEU 6: Neurogeneration & Alzheimer's disease

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Course
Neuroscience

Institution
Imperial College London (ICL)

Lecture notes from Imperial College London, Medical Biosciences BSc, 2nd year, Neuroscience (NEU) module. One of the great health challenges of our times is to cope with the increasingly prevalent age-related disorders as life expectancy rises globally. Neurodegenerative diseases are among the m...

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Uploaded on October 5, 2023
Number of pages 8
Written in 2022/2023
Type Class notes
Professor(s) Laura canevari
Contains All classes

neurology
neuroscience
neurogeneration
alzheimer
disease
disorders
neurodegenerative
nervous system
condition
cell death
dementia
amyloid
sporadic
therapeutic
treatment
familial
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Institution
Imperial College London (ICL)
Education Unknown
Course
Neuroscience

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Neuroscience module Imperial College London

R 1.641,19 R 845,25 9 items

1. Class notes - Neu 1: nervous system anatomy
2. Class notes - Neu 2: the development of the nervous sytem
3. Class notes - Neu 4: cerebral ischaemia
4. Class notes - Neuroscience vocabulary + syndromes
5. Class notes - Neu 6: neurogeneration & alzheimer's disease
6. Class notes - Neu 8: seizures & epilepsy
7. Class notes - Neu 5: learning and memory
8. Class notes - Neu 7: somatosensory system - chronic pain
9. Class notes - Neu 7a: somatosensory system - chronic pain
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Neurogeneration & Alzheimer’s disease
What is neurodegeneration?
- progressive loss of function or structure of neurons, and neuronal death CLIPs and HSPs m
- main risk factor = increasing age promote correct folding
- causes and pathogenic mechanisms are often unknown associated with unfolded proteins (pb
- progressive, get worse slowly over time ER...) => response leads to cell death
- drugs to treat symptoms but no cure “unfolded p response”: autophagy/ proteasomes
- accumulation & aggregation of specific abnormal p, mitochondrial damage, glial activation, ROS...

- lesion in spinal cord:
=> Amyotrophic Lateral Sclerosis (ALS) = motor neuron disease (MND): Stephen Hawking
=> affect both lower motor neurons & upper motor neurons: degeneration => denervation
=> weakness in muscles of limbs/ those to breath, swallow, speak (no effect mental function)
=> result in loss of all voluntary movements (progressive) + excitotoxicity

=> death from respiratory failure or lung infection + spasticity

=> 10% inherited mutation in SOD1 enzyme - 90% sporadic (random, unknown cause)

- lesion in the cerebellum
=> Olivo-ponco-cerebellar degeneration/ Friedreich’s ataxia (spinocerebellar ataxia)
=> ataxias (lose control and coordination of voluntary movement)
=> disturbance in gait (= démarche), balance, speech, eye movement BUT no weakness
=> Friedreich’s: recessive mutation in mitochondrial p frataxin
=> lesion sensory spinal structures & cerebellar nuclei

- lesion in the basal ganglia: abnormal movements
=> Parkinson’s disease (PD)
=> loss of dopaminergic neurons in the substantia nigra pars compacta
=> slow & stiff voluntary movements (eventually cease) - tremor
=> Huntington’s disease (HD)
=> CAG repeat in huntingtin gene => death of inhibitory GABAergic neurons in corpus striatum
=> involuntary uncontrolled, exaggerated movements: ‘chorea’
then, hypokinesia (Parkinson’s disease-like symptoms) - dementia

, - lesion in the cerebral cortex
=> Alzheimer’s disease (AD)

Neuronal death in neurodegeneration genetically programmed self-
digestion to survive starvation
- neurodegeneration progresses slowly => no necrotic cell death
=> excessive programmed cell death (clean removal of the cell): apoptosis or autophagy
=> remove damaged/ malfunctioning cell components via activation of genes & TFs
=> cell do not lyse & only a few degenerating neurons at the time
=> abundance neurons => clinical signs only when large part degenerated => can’t compensate
=> cellular stresses (aggregated p, mitochondrial damage, ROS) are triggers

What is dementia?
- neurodegeneration cerebral cortex => impairment higher cognitive functions

memory, spatial awareness, language, personality,
judgement, emotions, abstract thoughts...

- dementia = progressive loss of memory + at least 1 other function, interfering w/ everyday activities
=> reversible (alcohol abuse...)
=> irreversible (neurodegenerative diseases)

Types of dementia:
- AD: cause of 50-80% dementia cases
=> cortical degeneration w/ a specific pattern of pathological features
- vascular/ multi-infarct dementia: caused by many small strokes
a-synuclein
- dementia w/ Lewy bodies: accumulation of an aggregated p => troubles come & go (hallucinations..)
- frontotemporal degeneration: loss of language & behavioural change in a young pop
- Parkinson’s & Huntington’s diseases

- early manifestation w/ mild cognitive impairment (impairment performance complex everyday tasks)

Alzheimer’s disease (AD)
- first described in 1906 by Aloïs Alzheimer

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