Alzheimer’s Disease: An Updated Overview of Its Genetics

Abstract

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.

Evaluation of the Oral Bacterial Genome and Metabolites in Patients with Wolfram Syndrome

“…However, in the present study, P. gingivalis was not found, while several other bacterial genera, including abundant Gram-negative bacteria, were identified as differentiating WFS patients from other study groups. It is important when considering that both other oral pathogenic bacteria and gut microbiota may also be involved in various types of human neurogenesis [ 14 , 29 , 30 ]. Then, the present study selected the metabolites in GCF such as lactic acid, benzoic acid, and acetic acid, the intensities of which were significantly higher in WFS patients compared with both T1DM and healthy subjects.…”

“…Thus, these data suggest important genetic-environmental interactions between the presence of oral bacteria and a specific genetic predisposition to neurodegeneration or changes in gene expression in conditions where periodontal disease is a contributing factor [ 12 , 13 ]. Furthermore, the identification by GWAS of polymorphisms associated with various environmental factors may, as in AD, encourage the development of diagnostic and therapeutic strategies [ 14 ].…”

The MET growth signaling complex drives Alzheimer’s Disease-associated brain pathology in aged Shugoshin 1 mouse cohesinopathy model

“…The remaining 95% of human AD is late onset (LOAD) [1]. Although frequently-mutated genes are being identified and the effects on LOAD development are being assessed (e.g., [2,3]), the exact cause of LOAD remains unclear, and LOAD is considered multifactorial. With the lack of mechanistic understanding on the development, the intervention drug for LOAD has not been available in clinic.…”

Controlling the Impact of Helicobacter pylori-Related Hyperhomocysteinemia on Neurodegeneration

“…Recently, genetic polymorphisms in genes that have been implicated in AD, a primary neurodegenerative disease and the most common cause of dementia worldwide [ 85 ], include, among others, ABCA7 [ 86 ], PICALM [ 87 ], CLU [ 88 ], SLC24A4/RIN3 [ 89 ], ECHDC3 [ 90 ], MTHFR [ 91 ], as well as in insulin signaling such as INSR [ 92 ]. MTHFR mutations are associated with homocysteinemia, and increased homocysteine blood levels are considered to be an independent risk factor of cerebrovascular incidents.…”