that indicate the disease- and the affects of interventions
Applicable technologies (both
humans and animals)- MRI,
EEG
Use human tissue for lab exp
Better animal models
Approaches
Pathology to drug
novel drug
Reverse translation
improve current drug
Animal models
Categories
Developmental
Drug-induced
Lesion
Genetic
transgenic manipulations
AD
Disease mortifying- Develop drugs
that interfer with disease mechanisms
Sequence genes of
familial mutations
Animal models
Transgenic
overexpression of APP
models familial mutations (only 10%)
High levels of soluble Ab, Ab plaques,
Memory deficits, elevated b-secretase
Deficits in LTP (in some
labs)- not representative
No perfect model
95% AD cases are sporadic
elevated amyloid levels
from early age point- not necessarily in AD
No NFT
No neurodegeneration
Cannot test neuroprotective
(against neural loss) in most
See 4/5xFAD
APP + PS1 overexpression
APP + PS1 + tau
NFT
Ab diposition
No neuronal loss
5xFAD
aggressive Ab
reduced synaptic staining
neuronal loss
4xFAD
aggressive Ab
massive neuronal loss
Transgenic rats
cleverer than mice, but
less well characterised
Primates
Biologically closer to humans
Clinical trials
require long clinical trials to
see effects of progression
improved cognitive tests
disease biomarkers- Ab
Non-invasive Ab measurements required
PET- metabolic changes
Blood/urnine- not good
CSF- better- invasove
Parkinsons
Schizophrenia
Depression
Epilepsy
SE
Anotações:
a prolonged seizure (termed status epilepticus or SE) is induced by either electrical stimulation or a chemoconvulsant, leading to injury as the “initial precipitating event.”
kainic acid
Anotações:
chemconvulsant-induced SE models
pilocarpine
Anotações:
chemconvulsant-induced SE models
Limitations
Construct validity
Replicate the
underlying biology
Face validity
Reflect the
symptoms in man
Predictive validity
Predict treatments which will be
effective in the human condition