Transgenic mouse models of AD have been created to express the major pathological hallmarks of the disease, more specifically the amyloid_plaques , the neurofibrillary_tangles  and the substantial neurodegeneration  observed in patients. However, our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming cells from AD patients.
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1 Transgenic Mouse Models
The vast majority of these mouse models more specifically resemble the effects of Familial Alzheimer's Disease (FAD) mutations. Given the genetic complexity of AD, these include single, double, and triple transgenic mice that are able to express various disease-associated mutant forms of human amyloid_precursor_protein (APP), presenilin_1 (PS1), presenilin_2 (PS2), or tau. Transgenic mice have been able to recapitulate many, although not all, of the key features of AD at a behavioral and cellular level, and have been widely used in research for drug testing, treatment, and diagnostic purposes.
AD Mouse Models : Video showing how mice can be used to mimic Alzheimer's disease in humans
1.1. Modeling Amyloid PathologyFAD mutations in APP can be demonstrated in mice by overexpressing the human mutant APP. For instance the PDAPP transgenic mice line express mutant APP in various distinctive regions of the brain like the cortex, hippocampus, hypothalamus, and cerebellum . These transgenic mice also exhibit Aβ deposition and plaques in the cortex and limbic system, which are first observed at 3 months. Additionally, they show synaptic loss, inflammation, astroglial and microglial reactivity, and age-related cognitive impairments   . However, APP mice fail to reproduce the tau pathology and more importantly they lack substantial brain atrophy that is typically seen in cases of severe AD.
1.2. Modeling tau pathology
In order to model the neurofibrillary pathology in an AD model mouse scientists express transgenic human tau that contains mutations, which cause frontotemporal_dementia (FTD)  . However, tau mutations are not what causes AD, they are rather a contribution to the factors involved. Therefore, transgenic mouse lines expressing mutant human tau are used in conjunction with APP and then they are compared to lines that express the wild-type human tau. These models are called TAPP mice, and their utility is limited by early and significant motor deficits in the parent mice which can be seen as a confound to most learning and memory tests that are carried put to demonstrated AD behavioral deficits 
Nevertheless, there is another mouse model know as the 3xTg line which is created by combining mutant APP, PS1, and tau transgenes. The 3xTg mice are more appropriate to the study of AD because they develop extracellular plaques before the tangles, as is observed in human AD patients . However, these two pathologies appear to develop independently, without a causal link and this hinders the study of the underlying mechanisms.
1.3. Usefulness and Challenges
Although research on animals has contributed to our current understanding of AD, animals don't accurately reflect the features of the disease because the creation of animal models with substantial amyloid and tau pathologies, that are yet free of other confounding pathologies, remains a major obstacle in this field. Moreover, mice models are only able of reproducing the familial form of the disease, which represents approximately only 1%-6% of AD cases  and to date there are no murine models that can be used to study sporadic AD (see Alzheimer's Types), which makes up the majority of disease cases.
1.3.1. Early detection & diagnosis by measuring retinal cell apoptosisCurrently, there are no tests or exams that can accurately show whether a person has Alzheimer's. Even though physicians have proven to be very successful in determining if a person has dementia, the difficulty relays on determining the exact cause of that dementia. Therefore, clinical diagnosis of AD remains a postmortem one and this significantly hinders the possibility of prevention and even treatment of the disease. Recent research by Cordeiro et al., 2010  has taken advantage of the visual deficits, which have long been noted in AD patients to potentially use this as a tool for earlier diagnosis as well as a way of keeping track of the progression of the disease and the effects of treatment. This study was able to demonstrate in a transgenic AD animal model how fluorescent markers that attach themselves to the relevant cells can be used as a new technique that enables retinal cells, and therefore the stage of brain cell death, to be directly measured in real time. The retina is observed using a customized laser ophthalmoscope but this equipment can be applied in clinics worldwide, and it is an inexpensive and noninvasive technique.
2 Induced pluripotent stem cells (IPSCs) lines
2.1 Modeling the sporadic form (sAD) of the disease
This method consists of an optimized protocol that was initially developed by Vierbuchen et al., 2010  and it entails taking primary fibroblasts from patients with familial Alzheimer’s disease (FAD), and sporadic Alzheimer’s disease (SAD) and reprogramming them into induced pluripotent stem cells (iPSCs). Two recent studies   have examined how iPSCs can be used to model patient- specific AD pathology in vitro. In both of these studies iPSC lines have shown to differentiate into neurons that form functional synaptic contacts, exhibit normal electrophysiological activity, and express GABAergic and glutamatergic neuronal markers.
Neurons differentiated from these iPSCs where shown to have higher ratios of Ab42/Ab40, which is a characteristic feature of FAD. Those iPSCs derived from the APP patients and some of the SAD patient exhibited significantly higher levels of secreted Aβ40 as compared to controls . Also, changes associated with tau were observed in some of the phenotypes, indicating that iPSCs could be particularly useful for studying the true relationship between Aβ and tau in the development of AD. However, it is important to point out that the amount of neurons for each assay was relatively small and the process is very lengthy. Larger numbers of samples will be needed to understand altogether the different phenotypes of SAD in future studies.
3 Human Induced neuronal (hiN) cellsGroundbreaking laboratories are now looking into using human skin cells to create functional neurons. This has already been successfully accomplished by a group of researchers in Columbia University Medical Center, who were able to directly convert adult human fibroblasts to display a neuronal phenotype, and which they now call human-induced neuronal (hiN) cells . By using a combination of transcriotion factors such as Myt1l and other support factors, their study shows how human skin cells can become forebrain neurons without the need of [wikipedia: stem cells]. This direct conversion of cells method takes less time, is simpler because it requires cells that are easily obtained, and has a much higher reproduction rate.
3.1. Characteristics of hiN Cells
Qiang and collegues  were able to achieve about a 65% conversion efficiency (which is much higher than the one achieved with iPS cell technology) . of those cells that were successfully converted, about 85% of them contained the neuronal marker MAP2, and displayed morphological, electrophysiological, and gene expression profiles that resemble regular neurons. Furthermore, hiN cells display a forebrain glutamatergic neuron phenotype, and typical neuronal Na+, K+, and Ca2+ channel properties. To demonstrate that hiN cells can integrate into neuronal circuitry in vitro and in vivo, the researchers transferred the cells into embryonic mouse brains and examined them at day seven after the mice were born. They found that the neurons were capable of sending and receiving signals in both the CNS of mice and in laboratory culture.
3.2. hiN Cells of: Healthy Individuals v.s. Patients with AD
Neurons made from skin cells of 3 people with FAD, who had mutations in either PS1 or PS2 were compared with neurons made from healthy individuals and it was observed how the cells processed and localized of amyloid precursor protein (APP). Not surprisingly, differences where detected when the hiN cells of the FAD patients exhibited an altered phenotype. Their neuronal cells had an increased concentration of amyloid beta, a greater ratio of Aβ42/Aβ40 and larger endosomes with an increased collection of APP, than did neurons from controls.
Their findings suggest that at least FAD can be tightly related to abnormal endosomal function, and it also establishes hiN cells as potential tool for drug screening, cell replacement therapy and to examine human mutations in their actual environment.