Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegenerative disease that causes progressive and disabling impairment of cognitive functions including memory and attention. Alzheimer’s disease is also characterized by neuropsychiatric symptoms like apathy, social withdrawal, disinhibition, agitation and psychosis. Later stage symptoms also include sleep disturbances and motor deficits like dystonia, akathisia and parkinsonian symptoms. AD is now the sixth leading cause of death in the United States, representing a significant unmet medical need.
At Transpharmation, our multifaceted approach combines the use of naturally occurring deficits in aged animals along with pharmacological intervention to mimic aspects of the disease such as cognitive deficits, and sleep disruption. Furthermore, using our extensive biomarker platform we can profile translational disease markers such as TAU/phospho-TAU in rodents and assess the role of neuroinflammatory markers, such as cytokines, chemokines and microglia in AD disease pathology.
Examples of assays we offer:
- Biomarker analysis
- Delayed matching/non-matching to position tasks in aged rats
- Hyperlocomotion (a proxy for psychosis or agitation)
- Temporal deficit and pharmacological-induced deficit novel object recognition test
Models
Alongside the models below, we offer neuroinflammation modeling in vivo (e.g., LPS), a scopolamine-induced model of reduced cholinergic tone, and transgenic mouse models of tauopathy and amyloidopathy.
Canine amyloid-β is identical to the human protein, and aged dogs naturally deposit it in diffuse plaques that follow the human pattern over a 3 to 4 year window. Cognitive deficits track that deposition, so the model can test whether an intervention slows or halts amyloid pathology alongside its effect on cognition.
Read the full description: Aged canine model of late-onset Alzheimer’s disease
ARTE10 mice carry human APP with the Swedish mutation and mutant presenilin 1, giving a translational model of amyloid progression. We are characterizing its behavior and biomarkers across early, middle and late stages of amyloid pathology, starting with data at 5 months.
Tailored studies in rodents and dogs screen potential therapeutics for symptomatic and disease-modifying effects, taking a candidate from early proof of concept to a characterized clinical candidate across species.
The Morris water maze tests spatial learning and memory through hidden-platform acquisition and probe trials, detecting age-dependent cognitive decline in rodents.
The P301L Tau (JNPL3) transgenic mouse models progressive tau pathology, with increased total and phosphorylated tau in the brain and increased NfL in plasma and CSF.
Platforms used
Molecular Biomarkers & Histology Molecular biomarkers and tissue biomarker expression
Electroencephalography (EEG) In-vivo rodent telemetry
MoSeq AI-powered motion sequencing
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Cognitive Assessment Aged-dog memory and cognitive decline
Transgenics Genetically modified mice
Have a program in mind?
Talk to a Transpharmation researcher about your study design and timelines.