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

AD, the most common neurodegenerative disease, studies, enabling the assessment of the same animal
causes dementia in an irreversible and progressive at multiple time points and under various conditions,
manner. It is characterized by the presence of beta- thereby bolstering statistical power and minimizing
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amyloid (Aβ) protein aggregates and intraneuronal the number of animals needed. However, an inherent
neurofibrillary tangles (NFTs), in addition to significant issue arises from the extensive array of available animal
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neuroinflammatory and metabolic alterations. Clinically, models, with new models continually being developed.
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AD is diagnosed by the loss of declarative memory, Consequently, selecting the appropriate animal model for
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cognitive impairment, and behavioral and motor changes. research necessitates careful consideration of factors such
PD ranks as the second most common neurodegenerative as the animal’s background, the research objectives, and
disease in the elderly. It is characterized by the progressive the resource availability. In this article, we systematically
degeneration of dopaminergic neurons in the substantia reviewed recent literature on AD and PD to identify the
nigra pars compacta (SNc) and the accumulation of most frequently used rodent models for these diseases.
α-synuclein (α-Syn) aggregates (Lewy bodies) in the Our objectives were threefold as follows: (i) to enumerate
brain. Motor symptoms of PD include bradykinesia, all rodent models used in the last 5 years for AD and PD;
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resting tremors, gait disturbances, postural instability, (ii) to highlight and briefly describe the predominant
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akinesia, and muscle rigidity. Non-motor symptoms, genetic and induced models for these diseases; and (iii) to
such as cognitive decline, depression, anxiety, hyposmia, provide insights that will assist future investigations in
sleep disorders, hallucinations, and dementia, are also selecting the most appropriate rodent model for specific
present. 11,12 At present, there is no cure for AD or PD, and research goals.
the exact causes of their onset remain unclear. Therefore, 2. Search strategy and selection criteria
developing new treatments for the symptoms is urgently
needed. The use of models that mimic the symptoms and/ A literature systematic review was performed using the
or the pathophysiology observed in AD and PD patients is PubMed database on November 13, 2023. Two independent
clearly necessary. searches were performed. In the first search, the keywords
“animal model,” “mouse model,” “mice model,” and
Reports from Egyptian, Greek, Arabic, and Chinese
civilizations describe the use of animals to consolidate the “Alzheimer’s disease” were used. For the second search,
the keywords “animal model,” “mouse model,” “mice
knowledge of anatomy, physiology, and even rudimentary model,” and “Parkinson’s disease” were used. Filters “[Title/
surgeries. Much has changed since that time, and the use Abstract]” were applied, with a timeframe ranging from
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of animals in research has gained popularity. The creation 2019 to 2024; however, only studies published between 2019
of professional organizations and societies, along with the and 2023 were included. Specifically, only studies focusing
establishment of regulations, committees, and guidelines, on rodent models were considered, and data related to the
has contributed to the consolidation of animal experimental model type were extracted. Articles were initially screened
research. Since the development of animal models in a based on title and abstract, with full-text access utilized if
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controlled environment was established, rodents have been necessary. Studies were classified as “not clear” if essential
extensively used due to their fast reproductivity rate, small information remained ambiguous even after accessing the
size, short life cycle, and ease of manipulation, offering full text.
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remarkable advantages. Rodents have also been used as
models of human diseases, including neurodegenerative 3. Most used PD models
diseases such as AD and PD. These models were created
based on two main approaches: genetic modifications and The search yielded 1,624 studies (Figure 1). After removing
drug/toxin injections. Both methods can recapitulate some duplicates and adjusting the year range, 1,611 articles were
of the pathological hallmarks of the diseases, making them screened for eligibility. Exclusions comprised human
studies (n = 14), studies not involving rodent models
useful for studying pathomechanisms and identifying new (n = 43), studies unrelated to PD models (n = 195), and non-
therapeutic targets. 15
original articles (n = 137). Of the 1,222 included studies,
As models, animals cannot recapitulate all the aspects 954 (78.1%) studies used induced models, 239 (19.6%)
of the human condition. They usually exhibit only studies used genetic models, 18 (1.5%) studies used both
some aspects of a disease, which can be very helpful in models, and 11 (0.9%) used a combination model of two
developing new hypotheses and testing the efficacy of different PD models in the same animal (Figure 2A).
new drugs. Another valuable characteristic of animal The temporal trend over the past 5 years is depicted in
research is the ability to use individual baseline controls. Figure 2B. Figures 2C and D illustrate a total of 1,255 PD
This ability is particularly advantageous in longitudinal models used during this period, comprising 981 (78.2%)

Volume 3 Issue 3 (2024) 2 doi: 10.36922/an.2903