Model of Alzheimer’s Disease (AD) 

Dementia, one of the age-related devastating neurodegenerative diseases, is the leading cause of disability in the elderly population. Alzheimer’s disease (AD) is the most common type of dementia (60~80% of all cases). The main symptoms of Alzheimer’s disease are progressive and irreversible loss of memory, speech, reasoning, and cognition. The defining pathological hallmarks of AD include the accumulation of two key molecules, extracellular amyloid plaque and intracellular tau proteins in the brain. There is no treatment that cures AD, and the current available drugs may modestly modify symptoms. Greentech provides multiple animal models of Alzheimer’s disease for studies of AD pathogenesis and assessment of therapies.

Figure 1. The major pathological hallmarks of Alzheimer's disease (Götz et al., 2018)

Our Models of Alzheimer's Disease

1. APP/PS1 Transgenic Mice

The APP/PS1 double transgenic mice overexpress mutant human amyloid precursor protein (APP) and mutant human presenilin 1. Both mutations are linked to early-onset Alzheimer's disease. The APP/PS1 mouse model of AD is commonly used for studies of amyloid deposition, which shows age-dependent and region-specific progression of Aβ deposition, accompanied by increased microglial activation and astrogliosis.

Applications: to investigate pathogenesis of amyloid deposition and the efficacy of therapeutic approaches targeting Aβ deposition

Limitations: phosphorylated tau protein have been observed, but no mature neurofibrillary tangles (NFT)

2. SAMP8 Mice – Spontaneous Senescence Model

The senescence‐accelerated mouse prone 8 (SAMP8) strain displays early senescence, early deficits in learning and memory, tau and amyloid precursor protein (APP) transcriptional machinery. The SAMP8 mice have been widely used in aging research such as brain atrophy.

Applications: suitable for pathogenesis and pharmacology studies in the field of AD and other aging diseases

Limitations: high cost, scarce tau pathology

3. Scopolamine Induced AD Model

Scopolamine is a competitive antagonist of acetylcholine that can antagnoize muscarinic acetylcholine (ACh) receptors, causing deterioration of central cholinergic neurons and memory and cognitive deficits. Single administration of scopolamine can induce significant learning and memory impairment, and 4-week administration can further induce increased Aβ and phosphorylated tau accumulation in the brain.

Applications: scopolamine-induced AD model is a useful pharmacological tool to study AD pathogenesis and assess of AD drugs.

Limitations: reversible memory and cognitive deficits; Scopolamine blocks the central M receptors in a nonspecific manner, and animal may develop adverse reactions that affect behavioral evaluation, such as anxiety and increased voluntary physical activities.

Animal Species

Mice, rats

Clinical Assessment

(1) Neurobehavioral testing: Morris water maze, step through test, novel object recognition, Barnes maze, social interaction test, open field, rotarod test, elevated plus maze

(2) Aβ detection: ELISA, IHC

(3) Tau protein detection: WB

(4) IHC: neurons, microglial cells, astrocytes, NFTs

(5) Detection of AChE, ChAT, Ach: ELISA (for scopolamine-induced model of AD)

(6) Neuroinflammation detection

(7) Oxidative stress detection

Case Study

Animal model of Alzheimer’s disease: APP/PS1 transgenic mice