NUPY6_Neurodegenerative Disorders Flashcards
Covers pathology of neurodegenerative disorders (20 cards)
Amyloidogenic pathway involves extracellular cleavage of amyloid precursor protein (APP) at which site
Beta secretase
Pathogenesis of Alzheimer disease involves accumulation of
- Amyloid
- hyperphosphorylated tau
How does accumulation of hyperphosphorylated tau cause Alzheimer disease?
Tau is a microtubule associated protein involved in axonal transport.
Hyperphosphorylation–>interferes with axonal transport–> neurona death
genes associated with Alzheimer disease
- Mutation in beta-APP gene on chromosome 21
- Mutation in presenilin1, 2
- Expression of epsilon4 isoform of the apoE gene
most common genetic risk factor for late onset Alzheimer disease
Expression of epsilon4 isoform of the apoE gene
Gross appearance of the brain in Alzheimer disease
Bilateral, symmetrical, cortical atrophy
narrowing of gyri, widening of uslci
Pattern of hydrocephalus associated with Alzheimer disease
Hydrocephalus ex-vacuo
Microsocpic morphology of Alzheimer disease
Neurofibrillary tangles
Neuritic plaques
Composition of a neuritic plaque
core of amyloid, periphery composed of dystrophic neurites
Describe this morphologic hallmark of Alzheimer disease
Neurofibrillary tangles
dementia
Parkinsonism symptoms
visual hallucinations
fluctuating cognitive status
diffuse distribution of cytoplasmic, round to elongated eosinophilic inclusions
Dementia with Lewy body disease
Composition of Lewy bodies
alpha-synuclein
Composition of inclusions in FTLD
tau
Clinical features of frontotemporal dementia
alterations in personality, behavior(loss of inhibition) and language (aphasias) preceding memory loss
Morphologic finding in Pick disease
Gross: atrophy of frontal & temproal lobes (knife-like gyri)
Microscopy: Pick bodies (round, homogeneous neuronal cytoplasmic inclusions)
Triad of Wernicke encephalopathy
Ataxia, nystagmus, ophthalmoplegia, confusion
Morphologic finding associated with Wernicke encephalopathy
Hemorrhagic necrosis of mamillary bodies
Can you identify the radiologic changes in Wernicke encephalopathy?
Symmetric hyperintensities in mamilary bodies and periaqueductal gray matter
mage D= periaqueductal gray matter
Image E= mamillary bodies
4 Thiamine dependent bicohemical reactions
TCA cycle:
1. Alpha ketoglutarate —->succinyl coA by alpha ketoglutarate dehydrogenase
2. Branched chain amino acid dehydrogenase
3. Pyruvate—>acetyl coA by pyruvate dehydrogenase
4. Transketolase (HMP shunt)
Why do alcoholics develop hypoglycemia?
During the steps involved in alcohol metabolism, a net decrease of NAD/NADH ratio in the liver occurs. This impacts 2 key steps in gluconeogenesis i.e. lactate to pyruvate and malate to oxaloacetate conversion leading to hypoglycemia.
