APP/PS1 Amyloidosis Mouse Model of Alzheimer’s Disease
The APP/PS1 double transgenic mouse overexpresses mutated forms of the genes for human amyloid precursor protein (APPsw) and presenilin 1 (m146L) and is used to study amyloid deposition. Generally, this mouse line exhibits an age-dependent and region-specific progression of amyloid deposition; accompanied by increased levels of microglial activation and astrogliosis with concomitant cognitive dysfunction and impaired LTP.
Cognitive Impairment in APP/PS1 Mice
Figure 1: Female APP/PS1 mice show spatial memory impairment as seen in the decreased spontaneous alternations in the Y-maze test (A), and decrease in freezing in the contextual fear conditioning test. (B) These mice also exhibit deficits in discrimination learning (C) which is more apparent during their dark cycle where increased activity is also seen (D) using PhenoCube® system.
Figure 2: (Left Panel) Aβ was extracted from brains of 3, 7 and 12 months old WT and APP/PS1 mice. Insoluble Aβ40 and Aβ42 levels increase with age as measured by ELISA. (Right Panel) Inflammatory biomarker IL1β and IL-6 were increased in 8 months old APP/PS1 mice compared to WT mice.
APP/PS1 mice are characterized by a strong and progressive amyloid pathology with concomitant astrogliosis, microgliosis, synapse and neuronal loss. Within this scope we can offer a wide range of pathological markers. Synaptophysin or NeuN antibodies are used to detect morphological changes. Antibodies such as MOAB-2, LOC, 6E10, Aβ40/42 and dyes such as Thioflavin S (ThioS) recognizing different form of Aβ aggregates, are used to evaluate amyloid pathology. In addition, activation of microglial and astroglial can be measured by anti-CD11b and -GFAP antibodies.
Figure 3: (A) Typical 6E10 positive cortical plaque load. (B) LOC (AB2287) is specific to immature and mature amyloid fibers. (C) ThioS specifically stains to beta sheets in plaque cores. (D) Concomitant astrogliosis (astrocytes labeled by GFAP) around ThioS positive plaque cores (3D) at a hippocampal plaque.
Slice Electrophysiology – Long Term Potentiation
Using hippocampal extracellular field potential recordings in interface slices, PsychoGenics offers an evaluation of therapeutics designed to improve both pre- and postsynaptic function of APP/PS1 hippocampal CA3-CA1 synapse by evaluating basal synaptic transmission, including strength of excitation of pre-synaptic Schaffer collaterals, short- and long-term plasticity (paired pulse facilitation and LTP.
Figure 4: CA3-CA1 long–term potentiation (LTP) is impaired in 8-10 month old APP/PS1 mice. (A) A time-course of evoked responses (fEPSP slope normalized to the baseline) from an LTP study showing a deficit in APP/PS1 mice. (B) Summary of data taken from the last 5 minutes of recordings.*p<0.05 compared to WT mice.