**1. Introduction**

Alzheimer's disease (AD) is one of the major progressive and irreversible neurodegenerative diseases associated with aging [1]. The first case was identified by Dr. Alois Alzheimer in 1901 who presented the clinical and neuropathological characteristics of this disease on November 3, 1906 at the 37th meeting of the Society of Southwest German Psychiatrists in Tübingen, Germany [2]. AD is a progressively degenerative disease that destroys the patient's functional capacity and is the primary cause for loss of functional capacity among the elderly in devel‐ oped countries [3]. AD accounts for 60–80% of all dementia cases, as described in the Organi‐ sation for Economic Cooperation and Development (OECD) report. The number of people worldwide living with AD was estimated at between 27 million and 36 million in 2016 [4, 5]. AD symptoms worsen over time at a variable rate; on average; AD patients live between 4 and 8 years after diagnosis, but they could live until 20 years, depending on various factors. Once installed,three main stages of pathological progression of AD have been defined, namely early, middle and late.

In the early stage, a person may have memory lapses, such as forgetting familiar words or names, losing or misplacing a valuable object, or being unable to plan or organize. The middle stage is the longest and can last many years. The person with middle stage AD may confuse words, become easily frustrated or angry, and has increased difficulty expressing thoughts and performing routine tasks. In late stage or severe dementia, the person loses the ability to respond to the environment, to carry on a conversation and, eventually, to control movement; memory and cognitive skills continue to worsen, personality changes may occur and individ‐ uals need extensive help with daily activities [5]. According to the age of onset, AD can be classified as: early‐onset or familial AD accounting for only 5–10 % of AD cases, or late‐onset or sporadic AD accounting for the rest of the AD cases. Familial AD is associated with mutations in the genes for presenilin (PS) 1 and 2 and/or amyloid precursor protein (APP); its symptoms appear at 30–50 years of age, whereas the majority of sporadic cases develop after age 65 [6].

AD is a multifactorial disease that is a pathologically and etiologically complex. There are a few causative genes which have been linked to the relatively small proportion of patients with early‐onset familial AD [7]. The molecular analysis of families with early‐onset AD has made it possible to identify mutations in genes associated with the disease: APP, PS 1 and PS 2, and the mean onset age is 45. Mutations in Apolipoprotein E ε4 (Apo E ε4) genes are present in 15– 20% of AD cases appearing after 65 years of age. Three additional genes.

There are numerous hypotheses to explain the appearance of sporadic AD, such as head trauma, neuroinflammation, poor dietary habits and the lack of exercise, but the cause is still unknown [8, 9]. A possible explanation is that the abundant knowledge of AD biochemistry has not yet been well integrated into the cellular context of brain [10].

In order to elucidate the AD etiology, animal models that have genetic mutations linked to familial AD and show the same disease progression pattern have been developed. These models are either based on: (1) the overexpression of APP and secretases [11, 12]; (2) mutated APP [13, 14]; or (3) the overexpression of human APP (hAPP) together with mutated forms of PS [15]. Notwithstanding these mutations, such mouse models rarely develop neurofibrillary tangles (NFTs). To simulate tau pathology, a microtubule‐associated protein tau (MAPT) mutation associated with frontotemporal dementia is included in the 3xTg‐AD mouse, in which the expression of hAPP and mutated forms of PS and tau are combined [16, 17]. Currently, at least 11 rodent models that exhibit AD characteristics, such as Aβ accumulation, tau pathology, neuronal loss and pathophysiology of glial cells, are being studied [6, 18].
