Alzheimer’s disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1–5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or the Amyloid precursor protein (APP). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aβ) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.

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Some animal models, genetically modified (such as murine) and sporadic (as others species), enable the study of the origin of specific lesions observed in human neurodegenerative diseases. In particular, Alzheimer's disease (AD) models have been designed to test the hypothesis that certain lesions are associated with functional and morphological changes beginning with memory loss and impairment in activities of daily life. This review compares and evaluates the phenotypes of different AD animal models, on the basis of the specific objectives of each study, with the purpose of encompassing their contributions to the comprehension of the AD signs and symptoms in humans. All these models contribute to the comprehension of the human AD mechanisms regarding the heterogeneity of AD phenotypes: the overlap between AD and age-related changes, the variability of AD onset (early or late), the probable reactiveness of amyloid-β and tau proteins, the scarcity of senile plaques and/or neurofibrillary tangles in some AD cases, the spatial correlation of the pathology and cerebral blood vessels, and the immunological responses (microglial aging) and synaptopathy. Altogether, these considerations may contribute to find therapies to treat and prevent this disease.