(Answered 2022) ANA 442 Final Exam 100%
Verified
Alzheimer's prevalence
1/20 by 65, 1/2 by 85, most prevalent neurodegenerative disease
Impairments from AD
memory, cognition, other behaviors
Defined by atrophy, loss of neurons, loss of connections
Locations of plaques and tangles
intracellular tangles, extracellular plaques
seen in Cortex, hippocampus, amygdala
Neurofibrillary tangles
hyperphosphorylated tau
microtubule associated protein
messes up axonal transport
AB plaques
beta pleated sheets form aggregates
42
from B then gamma clevage of APP
extracellular domain
Amyloid precursor protein
APP
cellular funciton not really known, important for signalling events
AB: first cleave beta then gamma
Normal clevage: first alpha then gamma
Familial AD
mutations in APP (20 possible)
mutations in gamma secretase
increased aggregation and processing to produce 42
GAMMA SECRETASE BINDING SITE IS LOCATED WITHIN THE MEMBRANE
Helpful AD familial mutation?
A-T mutation at the beta secretase binding site
Swedish mutation
for AD
leads to more 42 than usual
more aggregations
alters the processing
at the beta secretase site
Presenillin 1 and 2
if mutated, causes AD
associated with the gamma secretase complex
, AB hypothesis
about 2% is early onset
not sure if AB is cause of disease, or the result of pathogenesis
ApoE risk factor
for AD
lipid transport and metabolism
found within the plaques
E4 allele- have more copies? get earlier onset AD
Other risk factors for AD
microglial dysfunction
Alzheimer's timeline
AB-Tau-Atrophy-memory-clinical findings
Pharmacokinetics
absorption, metabolism, secretion of drug
Pharmacodynamics
effects of drugs on target
Procedure for drug discovery
define pathogenesis of disease, select molecular target
test in cellular and biochemical assays
define candidates thru animal models
human testing
Phase 1: safety
Phase 2: proof of concept
phase 3: large patient population
proteinopathy
diseases associated with misfolded proteins
prions
proteinacious infectious particles
scrapie, Kuru, CJD
prion diseases caused
by propogation of protein-induced protein conformational changes
virus-like
Huntington's disease
Dominant inherited disorder
First published -1872 George
Huntington
Affects patients midlife
Depression, cognitive defects
Abnormal movements - targets
striatum
Characterized by CAG (polyglutamine)
repeats in Huntingtin protein
Poly-glutamine repeat
seen in HD, can be seen with many other diseases
Reserpine
Verified
Alzheimer's prevalence
1/20 by 65, 1/2 by 85, most prevalent neurodegenerative disease
Impairments from AD
memory, cognition, other behaviors
Defined by atrophy, loss of neurons, loss of connections
Locations of plaques and tangles
intracellular tangles, extracellular plaques
seen in Cortex, hippocampus, amygdala
Neurofibrillary tangles
hyperphosphorylated tau
microtubule associated protein
messes up axonal transport
AB plaques
beta pleated sheets form aggregates
42
from B then gamma clevage of APP
extracellular domain
Amyloid precursor protein
APP
cellular funciton not really known, important for signalling events
AB: first cleave beta then gamma
Normal clevage: first alpha then gamma
Familial AD
mutations in APP (20 possible)
mutations in gamma secretase
increased aggregation and processing to produce 42
GAMMA SECRETASE BINDING SITE IS LOCATED WITHIN THE MEMBRANE
Helpful AD familial mutation?
A-T mutation at the beta secretase binding site
Swedish mutation
for AD
leads to more 42 than usual
more aggregations
alters the processing
at the beta secretase site
Presenillin 1 and 2
if mutated, causes AD
associated with the gamma secretase complex
, AB hypothesis
about 2% is early onset
not sure if AB is cause of disease, or the result of pathogenesis
ApoE risk factor
for AD
lipid transport and metabolism
found within the plaques
E4 allele- have more copies? get earlier onset AD
Other risk factors for AD
microglial dysfunction
Alzheimer's timeline
AB-Tau-Atrophy-memory-clinical findings
Pharmacokinetics
absorption, metabolism, secretion of drug
Pharmacodynamics
effects of drugs on target
Procedure for drug discovery
define pathogenesis of disease, select molecular target
test in cellular and biochemical assays
define candidates thru animal models
human testing
Phase 1: safety
Phase 2: proof of concept
phase 3: large patient population
proteinopathy
diseases associated with misfolded proteins
prions
proteinacious infectious particles
scrapie, Kuru, CJD
prion diseases caused
by propogation of protein-induced protein conformational changes
virus-like
Huntington's disease
Dominant inherited disorder
First published -1872 George
Huntington
Affects patients midlife
Depression, cognitive defects
Abnormal movements - targets
striatum
Characterized by CAG (polyglutamine)
repeats in Huntingtin protein
Poly-glutamine repeat
seen in HD, can be seen with many other diseases
Reserpine
