#9 Acute and progressive neurodegeneration. AD/Stroke Flashcards
(18 cards)
What is a stroke?
Stroke is the sudden death of brain cells due to inadequate blood flow, leading to permanent neurological dysfunction. It can result from a blocked (ischemic) or burst (hemorrhagic) blood vessel.
What are the two major types of stroke?
Ischaemic stroke (85%): Blockage (e.g., thrombus, embolism, small vessel disease).
Hemorrhagic stroke (15%): Bleeding into or around the brain (e.g., aneurysm rupture, hypertension).
What are the clinical features of stroke?
FAST:
Face drooping
Arm weakness
Speech difficulty
Time to call emergency services
How is AD diagnosed?
Clinical/radiological assessment (80-90% accuracy)
Definitive diagnosis: Autopsy (identification of plaques and tangles)
What is the ‘penumbra’ in stroke?
It is an area of brain tissue with reduced blood supply but not completely infarcted, where neurons are at risk but still salvageable.
What happens at the cellular level during ischaemia?
Loss of ATP production
Ion pump failure (Na+/K+ pump)
Calcium overload
Glutamate excitotoxicity
Activation of degradative enzymes (calpains, lipases, endonucleases)
Necrosis in the core, apoptosis in the penumbra
How does hemorrhagic stroke differ clinically from ischaemic stroke?
Hemorrhagic stroke often has bilateral symptoms due to rapid haematoma spread, while ischemic stroke usually has unilateral symptoms.
What are the treatments for ischaemic stroke?
Alteplase (tPA): IV thrombolysis within 4.5 hours (after CT confirms no hemorrhage)
Mechanical thrombectomy: Within 24 hours
Preventative therapies: Anticoagulants (Warfarin), antiplatelets (Clopidogrel), statins, antihypertensives
What are the main pathological features of AD?
Extracellular β-amyloid plaques
Intracellular neurofibrillary tangles (hyperphosphorylated Tau)
Chronic neuroinflammation (astrocytes, microglia activation)
Oxidative stress
Why is the Circle of Willis important in stroke?
It provides collateral blood flow; congenital anomalies are common in stroke patients.
What are treatments for hemorrhagic stroke?
Surgical interventions: Coiling, clamping, craniotomy
Manage blood pressure to prevent further bleeding
What characterizes neurodegenerative diseases like Alzheimer’s?
Progressive selective neuronal death, protein aggregation (misfolded proteins), inflammation, oxidative stress, excitotoxicity.
What is the role of Tau protein in AD?
Hyperphosphorylated Tau forms neurofibrillary tangles, destabilizing microtubules and leading to neuronal dysfunction and death.
What is the role of β-amyloid in AD?
Forms plaques
Soluble β-amyloid oligomers are particularly neurotoxic via PrPc signaling
Activates kinases (Fyn, p38, JNK), impairs synaptic plasticity and Aβ clearance
What are the genetic risk factors for AD?
Familial (early-onset): Mutations in APP, presenilin 1/2
Sporadic (late-onset): ApoE ε4 allele increases risk; TREM2 mutations impair microglial Aβ clearance
How does hippocampal atrophy relate to AD symptoms?
Loss of cholinergic neurons projecting to the hippocampus leads to memory loss and cognitive decline.
What treatments are available for AD?
Symptomatic: Cholinesterase inhibitors, NMDA receptor antagonists
Disease-modifying (under research):
γ-secretase inhibitors
Anti-Aβ antibodies
Anti-inflammatory therapies (e.g., TREM2 antibodies)
Neuroprotection (e.g., antioxidants)
Regenerative approaches (NGF, BDNF, stem cells)
Why is sporadic AD challenging to treat?
Because the exact cause remains unknown and multiple overlapping pathologies contribute to neuron death.
