L18 - Neurodegeneration Flashcards
What are neurodegenerative disease?
Disorders characterised by progressive degeneration or loss of neurons, leading to cognitive, motor and functional impairments
What are some common neurodegenerative diseases
Alzheimer’s Disease (AD)
Parkinson’s Disease (PD)
Huntington’s Disease (HD)
Multiple Sclerosis (MS)
Amyotrophic Lateral Sclerosis (ALS)
What are transmissible spongiform encephalopathies (TSEs)?
Fatal brain disease caused by prions, such as Creutzfeldt-Jakob Disease (CJD) and Bovine Spongiform Encephalopathy (BSE or mad cow disease).
How do prions cause disease?
Prions are infectious proteins that replicate by converting normal cellular proteins into abnormally folded copies, leading to brain damage.
What are symptoms of Creutzfeldt-Jakob Disease (CJD)?
Personality changes
memory loss
impaired thinking
insomnia
jerky movements
rapid mental deterioration.
What are the 4 major human prion diseases?
Creutzfeldt-Jakob Disease, Gerstmann-Sträussler-Scheinker Syndrome, Fatal Familial Insomnia, and Kuru.
What are the main phases of Alzheimer’s Disease (AD)?
Preclinical AD: Abnormal biomarkers, no symptoms.
Mild Cognitive Impairment (MCI): Cognitive decline without impaired daily living.
Dementia: Progressive loss of cognitive and functional abilities.
What are the histopathological hallmarks of Alzheimer’s Disease?
Extracellular amyloid-beta plaques and intracellular tau tangles.
What imaging techniques are used to diagnose Alzheimer’s Disease?
CT, MRI, PET scans, and FDG PET to detect energy use abnormalities.
What biomarkers are analyzed in Alzheimer’s Disease?
Cerebrospinal fluid (CSF) levels of amyloid-beta 42 and phosphorylated tau.
What is the amyloid hypothesis?
Alzheimer’s is driven by the accumulation of amyloid-beta plaques that disrupt neuronal function.
What is the tau hypothesis?
Alzheimer’s progression is linked to the spread of tau protein tangles.
What are the stages of tau tangle progression?
Stages I-II: Entorhinal cortex and locus coeruleus.
Stages III-IV: Hippocampus and parts of the neocortex.
Stages V-VI: Extensive spread throughout the neocortex.
Name some amyloid-reducing drugs and their effects.
Aducanumab: FDA-approved, reduces amyloid-beta plaques but with uncertain clinical benefits.
Donanemab: Slows cognitive decline by 30–35%.
Lecanemab: Slows cognitive decline by 27%.
What are common side effects of amyloid-reducing drugs?
Brain swelling, small bleeding, headache, dizziness, and nausea.
What causes Parkinson’s Disease?
Degeneration of dopamine-secreting neurons in the substantia nigra, affecting the nigrostriatal pathway.
What are the core motor symptoms of Parkinson’s Disease?
Tremor, bradykinesia (slowness of movement), and rigidity.
What behavioral symptoms are associated with Parkinson’s Disease?
Anxiety, depression, sleep disorders (e.g., REM sleep behaviour disorder), and mood changes.
What is the pathological hallmark of Parkinson’s Disease?
Lewy bodies containing the protein alpha-synuclein
How does dopamine replacement therapy help Parkinson’s patients?
It alleviates motor symptoms by supplementing dopamine levels.
What is the “prion paradigm” in neurodegenerative diseases?
Misfolded proteins like amyloid-beta, tau, and alpha-synuclein propagate neurodegeneration through aggregation and spread.
How does neurodegeneration progress in Alzheimer’s Disease?
Tau tangles spread from the entorhinal cortex to the hippocampus and eventually to the neocortex.
How does neurodegeneration progress in Parkinson’s Disease?
Alpha-synuclein spreads from the substantia nigra to other brain regions, causing motor and cognitive dysfunction.
Why is early diagnosis of neurodegenerative diseases important?
Early intervention can slow progression and improve quality of life.
