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Advanced Neurology Alzheimer’s and Parkinson’s disease rodent models

Figure 3. PRISMA flow diagram for systematic review conducted on Alzheimer’s disease animal studies from 2019 to 2023

4.1. Genetic models peptides. PSEN1 potentially holds a significant role in
4.1.1. APP/PS1 development, as evidenced by knockout mice displaying
severe abnormalities and a shortened lifespan. However,
The APP/PSEN1, APPPS1, or APP/PS1 mouse is among mouse models featuring pathogenic PSEN1 mutations
the most used transgenic AD models. These animals remain viable when crossed with strains carrying human
harbor the human transgenes for the amyloid precursor mutant APP, as demonstrated in the APP/PS1 model, in
protein (APP), specifically in the form of the Swedish which the amyloid pathology is intensified. 80
mutation (APPswe), and for the presenilin 1 (PSEN1)
with an L166P mutation, both regulated by the Thy1 The onset of AD features in mice occurs progressively
promoter. Initially identified as genes linked to autosomal- with age. Amyloid plaque deposition initiates in the
dominant AD, presenilin is an expansive multi-pass neocortex around 6 weeks, followed by the hippocampus
transmembrane protein that forms the catalytic core of at about 3 – 4 months. Subsequently, depositions in the
the γ-secretase complex. This complex cleaves various striatum, thalamus, and brainstem become apparent
integral membrane proteins, notably APP, the protein at 4 – 5 months of age. In addition, phosphorylated tau-
whose proteolysis generates Aβ peptides. Most pathogenic positive neuritic processes (another AD biomarker) are
APP mutations tend to cluster around the cleavage sites observed in the proximity of amyloid deposits, although
of proteases (especially γ-secretase), generally resulting no fibrillar tangles have been described in this model.
in elevated Aβ levels. Besides its role in Aβ generation, Behavioral manifestations, including cognitive and memory
APP is implicated in diverse functions such as gene impairments, become evident around 7 months of age. 81
expression regulation, response to neuronal damage, and 4.1.2. 5×FAD
neuronal and synaptic adhesion during development.
In addition, its extracellular cleavage product sAPPα The 5×FAD mice present five mutations that express
exhibits neurotrophic properties. On the other hand, the human APP and PSEN1, namely the Swedish (K670N/
79
primary pathogenic mechanism of presenilin mutations M671L), Florida (I716V), and London (V717I) mutations
involves subtle alterations in cleavage steps, leading in APP, and the M146L and L286V mutations in PSEN1.
to the generation of longer and more aggregating Aβ This model presents intraneuronal immunoreactivity for

Volume 3 Issue 3 (2024) 8 doi: 10.36922/an.2903