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38 Cards in this Set
- Front
- Back
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Neurodegenerative disorders in Older ppl
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-Cognitive impairment
-Dementia -Motor slowing -Impaired mvt -Instability -Falls -Gait disturbance -Sensory disturbance(visual,auditory) |
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AD is assoc. with
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-APP and A beta amyloid
-senile plaques -amyloid angiopathy with AB amyloid pz |
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CJD assoc. with
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-Spongiform change assoc. with Prion protein
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ALS/MND
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Superoxide dismutase
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Parkinson's Disease
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-Lewy bodies composed of Alpha synuclein seen in Parkinson's in Diffuse Lewy Body Disease
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Huntington's Disease assoc. with
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Huntingtin/PolyQ
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Frontotemporal dementias
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-neurofibrillary tangles (tau pz aggregates) & Pick's bodies may be present assoc. with swollen(balloned) neurons.
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In AD,patho. changes seen in
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Temporal and Parietal regions
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Lewy Body dementias lead to patho. changes predominantly in
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Frontal lobes
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In PD,
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Substantia nigra and striatum particularly affected
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Risk factors for AD
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-AGE(exponential doubling of prevalence of AD with each decade after 50 yo)
-chrm 19(Apolipoprotein E) |
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4 basic types of AD
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-Amnestic(temporal-affects memory & spares primary sensory + motor areas)
-Visuospatial(R>L) -Aphasic(L>R) -Frontal |
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APP
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Amyloid precursor molecule
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Amyloid secretase cleaves APP tucked in cell membrane into
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-Amyloid A beta
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AB amyloid changes from alpha
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To Insolube beta sheets
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AB amyloid protein
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-40-42 A.A
-histidine residues that can bind to Cu2+ and Zn2+ |
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As Amyloid protein comes out of lipid layer,
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it changes into Beta Sheets.
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11 C-PIB
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new biomarker that acts as a ligand and is an analogue for old dyes that bind to amyloid pz + radioactive Carbon.(ligand sits in brain for 30 min)
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Detect MCI using
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Psychometric measurements
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Around what age the AD process starts?
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-50 y.o
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What is the peak age at onset and disability for DEMENTIA ?
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80 y.o
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MCI starts around
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70 y.o
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Subacute evolution of dementia
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From onset to death= 3-6 months
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BSE in
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Cattle (CJD in humans)
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CJD
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Rate of 1 in a million all over the world.(10 %)
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In Australia,there are
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20 cases of CJD in whole population.
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Kuru ppl
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-Cannibalism
-Papua NewGuinea |
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Brain tissue in BSE
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changes mimic scrapies
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BSE in US
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Chronic Wasting Disease
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Spongiform change(squirrel monkey)
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-Small minute vacuoles
-Subacute Spongiform encephalopahty -Swelling of mito -Reaching to abnormal pz |
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If you inherit mutation in PrP,
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guarantee to get disease in next generation
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normal isoform of PrP has t1/2 of
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30 min
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Abnormal isoform of PrP
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-Abnormal B sheet conformation(pair up with alpha helices-->induce pz to fold in beta sheet--> sticky in brain.
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vCJD
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-young individuals in their 20s presenting with psychiatric disorders
-median age at death=28 -median age at onset=26 -median duration of illness=14 months -slight excess of males over females -all cases are MM at codon 129 of PRNP gene |
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vCJD immunocytochemistry
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-diagnosed as presence of pz in reticulolymphoid system
-accum. in lymphoid follicles -Propensity to replicate in reticulolymphoid system |
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Cant donate blood if lived in UK between
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1980-1996
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vCJD blood is
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Infectious(sCJD too)
-estimated incubation is 6-15 yrs -human to human passage cohort might be evolving with a peak in 2020. |
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Lewy bodies
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-Round bodies sitting in cytoplasm
-Aggregated pz in substantia nigra |
