LMP299Y1 Lecture Notes - Neurodegeneration, Motor Neuron, Inclusion Bodies

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6 May 2014
School
Course
Professor
LMP410
September 11, 2013
Each quiz is one percent – ten quizzes, one per lecture – five minutes – on what was just heard
Midterm is worth 40% - only up to ALS lecture
Final exam is from ALS lecture – NOT CUMULATIVE
Understand what you are hearing – so can apply to question
Neurodegenerative Diseases: Common properties and strategies
A neurodegenerative disease – affects brain – deterioration of specific subset of neurons
Divided into two different groups – causing problems with motor function – the other affects
memory
This division is the classical definition
Classified by protein that is toxic, accumulates in brain and spinal cord
Repeat expansion of glutamines – toxic to proteins –
Amyloid depostited extracellularly
Tauopathies – tau protein, structural protein
ALS –
MS – demyelinating disease – see sclerotic plaques, multiple plaques hence name
Less common diseases – will hear a little of these
If patient goes to see doctor, get diagnosis of neurodegenerative disease – it is a PROBABLE
diagnosis
Only definitive when look at post-mortem examination
Alzhemiers – probable diagnosis only – can only be confirmed by neuropathologists after eath
Clinical – can be attributed to many different things, the symptoms – clinician uses rational
deduction – narrow down
Imaging techniques get better – MRI imaging sees structure of brain
Second to understand – diseases motor vs memory is classical definition – they are highly
heterogenous and motor disturbances in Parkinsons, patients can towards the end have
dementia
Pure alzheimer’s disease can also have motor problems in the end too
Common features
All age related – do not normally see neurodegenerative diseases in young people
Usually in aging population of forty and above
Pathological characteristics – neuronal death, and in each disease, the primary neuronal
pathway that diengerates is specific to that disease;
Second pathological characteristic – amyeloid formation – misfolded protein or on the other
side, get inclusion bodies within the cell – misfolded proteins that accumulate and cause toxicity
And all of the diseases have an inflammatory component
No known cure – and all diseases are lethal
All neurodegenerative diseases start in brain – can affect central and peripheral function – ALS
starts in the brain for degeneration – but degeneration of motor neuron – goes into peripheral
nerves as well – start in the brain but can also affect the peripheral neurvou system as well
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Dementia definition
Cognitive function
Loss of memory – loss of memory of things that are engrained
Orientation – where you are in relation to other things, where you are in space
Language – to retrieve the right words to express your thoughts
Perception – facial perception; events
Attention and concentration – ability to watch a whole movie
Ability to perform tasks in sequence – for instance, cooking, getting dressed (underclothes first,
clothes later)
Motor dysfunction
Tremors can be all the time or resting tremor (when hand is resting on top of table, not using
muscles, can have resting tremor)
Rigidity – lack of motor neuron innervation to muscles
Gait and posture disturbances – shuffling so do not have enough enervation to muscles – so
cannot take big step
Posture disturbances – movement disorders, can get hunched look because core muscles that
support upright posture – if motor neuron, goes to muscles and if muscles aren’t enervated, do
not have core strength – as disease progresses, you get things like brachkinesia, which is
slowness or absence of movement
Cognitive – signal to motor cortex is not making arm move
If do not exercise, muscle can atrohy ultimately
Speech –
Ronald Reagan
Probable Alzheimers
Exercise is good for people with memory disorders because stimulate neurons???
Rosa Parks
Sugar Ray Robinson
Alzhimers
Carlton Heston
Alzheimers
Alzheimers Disease
Hoarding behaviour – can hoard anything
If a patient has memory disorder, why go from walking around to lying in fetal position? In
Alzheimer’s disease, you lose everything you’ve ever learned – baby lies in bed in fetal position
– babies learn to eat, walk, talk, etc.
In 1906, Alzheimer’s critieria still the same used today to diagnose this as autopsy
Every 72 seconds – graphic of what happens in the brain
Prevalence of Alzheimer’s Disease
Alzheimer’s disease is related to age – percent of population with AD – sixty is small –
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