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

of age, APOE-deficient mice have been shown to develop derivative strain from the AKR/J mice lineage, the SAMP8
xanthomatous lesions in the brain, predominantly model, along with other SAMP (e.g., SAMP2, SAMP6)
consisting of crystalline cholesterol clefts, lipid globules, and SAMR (e.g., SAMR3) strains, each manifests distinct
and foam cells. In addition, studies indicate altered stress phenotypes. The natural occurrence of this model
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responses, synaptic damage, impaired spatial learning and confers an advantage over transgenic counterparts, as it
memory, and modified long-term potentiation in APOE- mimics sporadic AD, which comprises a larger proportion
deficient mice. In contrast, APOE KI mice are generated of AD cases compared to genetic familial AD. However,
by replacing exons 2, 3, and most of exon 4 of the APOE the precise genetic factors driving the accelerated aging
gene in the mouse with the human APOE gene sequence phenotype in SAMP8 mice remain elusive. 107
including exons 2, 3, and 4. However, a major disadvantage
of the model is its failure to develop the two main 4.2. Induced models
histopathologies of AD, rendering it non-specific for AD 4.2.1. STZ
pathology. Nonetheless, it remains relevant for studying STZ, derived from the bacteria Streptomyces achromogenes,
other aspects of the disease. Consequently, many studies is a glucosamine-nitrourea compound with clinical utility
opt for combined models, wherein APOE KO or KI mice as a cytotoxic agent in the treatment of neuroendocrine
are crossed with amyloidosis or tauopathy mouse models, pancreatic tumors. When administered intraperitoneally,
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facilitating the comparison of the effects of different human STZ has been documented to induce type 1 diabetes
APOE isoforms on AD-related pathology. 98-101 mellitus in animal models. Notably, intracerebroventricular

4.1.7. Tau injection of STZ, usually at a dosage of 3 mg/kg, has
revealed its ability to mimic aspects of AD. 109,110 STZ affects
Tau models, classified herein as transgenic models for the insulin-signaling pathway and glucose metabolism,
tauopathies, encompass variations that either overexpress leading to an insulin-resistant state within the brain. This
or express normal or reduced levels of human tau. disruption mirrors early AD pathology characterized
Tauopathies constitute a significant aspect of AD, rendering by glucose hypometabolism, insulin downregulation,
this model advantageous for studies focusing solely on this and resistance. In addition, the STZ-induced model
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pathological aspect of the disease. On the other hand, tau replicates other features of AD, including mitochondrial
hyperphosphorylation diverges from the amyloid theory, dysfunction, oxidative stress, and neuroinflammation.
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in which Aβ plaques precede tau hyperphosphorylation. Furthermore, STZ administration prompts Aβ aggregation
Consequently, the absence of the Aβ component may and increased tau hyperphosphorylation through elevated
pose a limitation to this model. The establishment of tau GSK3β expression, culminating in cognitive deficits
models generally involves modifying the microtubule- and memory impairment. 111,113,114 This model serves as a
associated protein tau (MAPT) gene or inserting the valuable tool for investigating insulin signaling impairment
human tau transgene. These animals exhibit cognitive in AD and late-onset AD, given its success in mimicking
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impairment and significant neuronal loss attributed to pathological hallmarks, especially those of sporadic AD.
tau redistribution to cell bodies and dendrites, alongside However, it is noteworthy that this model is associated
the hallmark hyperphosphorylation of tau, culminating with a high mortality rate. 115
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in NFTs. Illustrative examples within this model
classification include the hTAU, P301L, and M20 mice. 4.2.2. β-Amyloid
The majority of the selected studies involved the
4.1.8. SAMP8
administration of Aβ through intracerebroventricular
Considering that age stands as the main risk factor for or intrahippocampal routes, although other brain
AD, the SAMP8 offers a model featuring an accelerated regions, including the olfactory bulb, parietal cortex,
aging phenotype. This characteristic renders it relevant for entorhinal cortex, and striatum, have been suggested as
investigating several diseases in which the aspect of age is potential targets. Injectable Aβ exists in various forms
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considered, although it does not specifically replicate AD categorized by the number of amino acids and degree of
pathology despite its frequent use as such over the past pathogenesis. Among these, Aβ 1-42 is notably the most
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5 years. Notably, the model exhibits increased Aβ levels pathogenic in vivo, recognized for its role as an activator
in the hippocampus, beginning between 4 and 12 months, of neuroinflammation and oxidative stress, which induce
although without the appearance of senile plaques, a synaptic dysfunction and neurodegeneration. 113,117
hallmark of AD pathology. Behaviorally, these mice Intrahippocampal administration of Aβ 1-42 prompts an
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demonstrate impaired learning and memory between increase in the production of APP, consequently promoting
8 and 10 months of age. Originating naturally as a greater amyloid plaque deposition. Given that Aβ1-42
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Volume 3 Issue 3 (2024) 11 doi: 10.36922/an.2903