WEEK 4: Neurodegenerative Disorders Flashcards
General term for loss of memory and other mental abilities
severe enough to interfere with daily life; caused by physical
changes in the brain.
DEMENTIA
____________ considered the most
common cause of dementia worldwide (60%) and ________________ as the second commonest (30%).
AD, vascular dementia
the pathology of this is simply patients
having multiple or accumulated micro infarcts in different
parts of the brain that have been asymptomatic.
Vascular Dementia
main gross pathology here is atrophy of the brain. Simply
meaning that lot of neurons become dysfunctional, perceived
to be of no use and undergoes death through apoptosis.`
Dementia
The pathology associated with Alzheimer’s are of two lesions:
amyloid plaques and neurofibrillary tangles also known as tau tangles
mild cognitive impairment: where is the lesion?
Medial temporal lobe
Mild AD where is the lesion?
The dse spreads to lateral temporal and parietal lobes
Moderate AD where is the lesion?
Dse spreads to the frontal lobe
Severe AD where is the lesion?
Disease spreads to the occipital lobe
• Age related disease
• Progressive neurodegenerative disorder characterized by
cognitive decline and the presence of two core pathologies:
amyloid plaques and neurofibrillary tangles.
• Presence of a sustained immune response (chronic
inflammation) in the brain has emerged as a third core
pathology.
AD
Amyloid plaques vs neurofibrillary tangles?
Amyloid plaques accumulate outside the neurons
between the axonal connections but will eventually
interfere with the transmission of neuron signals.
Neurofibrillary tangles accumulate within the cytoplasm of
the neurons and cause a total dysfunction of the neuron.
• Integral membrane protein expressed in many tissues and
concentrated in the synapses of neurons
• Its primary function is not known
• Implicated as a regulator of synapse formation, neural
plasticity, antimicrobial activity, and iron export.`
Amyloid precursor protein (APP)
is the capacity of the brain to develop
complex neuronal connections. Transmission of neuron
signals is not linear; it’s circular.
Neural plasticity
critical initiator that triggers the progression of Alzheimer’s Disease
amyloid B peptide
T or F? The degree of clinical manifestation will depend on how much of the B amyloid has accumulated at synaptic junctions and the number of synaptic junctions affected
T
T or F AB peptide is a physiologic product,
T
Because of the chronic inflammation going on in the brain, microglial cells become dysfunctional. They now cannot remove the normal Ab amyloid physiologically produced T or F?
T
how does Amyloid B peptide accumulate?
- Caused by A overproduction or perturbation clearance or both
- A generated from amyloid precursor protein through sequential cleavage of and -secretases
- A removal is dependent on the proteolysis, lysosome degradation system and glial cells.
In a state of chronic inflammation, there is an over production of amyloid. Normal glial cells will be over exhausted and gradually become dysfunctional. To or F?
T
Chronically activated microglia release a variety of pro-inflammatory and toxic products, including
reactive oxygen species, nitric oxide, and cytokines
is the protein that is formed in the neurofibrillary tangle, but it is also a normal protein that we all have in our brain.
Tau
where is tau most abundant?
• It is most present in the axon of a neuron. In the axon, it is attached to the microtubules.
What is the major cytoskeleton of the neuron?
Microtubules
Neurofibrillary tangles are formed by ?
hyperphosphorylation of the tau protein, causing it to aggregate, or group, in an insoluble form.
