Identification of Associated Genes with Late-Onset Alzheimer’s Disease

Hereditary diseases are a condition that is passed from one parent to a child, the more recognizable being Sickle Cell Disease or Cystic Fibrosis.  Inherited diseases affect billions of people, from Central America to Northern Europe. One disease that can be hereditary, is known as Alzheimer’s Disease, also known as AD. Alzheimer’s Disease is a variety of dementia and is known to have two forms, based on age of development, early-onset, and late-onset: LOAD. People diagnosed with this ailment display symptoms of memory loss, confusion, impaired judgment, along with mood and personality changes. Loved ones that have to witness an AD sufferer are also at risk of developing that same disease. Research going into identifying the genes associated with Alzheimer’s can, in the future, contribute to discovering better treatments or even a cure to AD.

Prior to more resent research, there were two acknowledged genes linked to Alzheimer’s disease, a mutation in APP on the 21st chromosome, and an unidentified loci on the 19th chromosome. In the early 1990’s, this gene was classified as APOE, which was made up of three alleles, respectfully known as APOE-2, APOE-3, and APOE-4. A study by Corder, E H  et al in 1993 discovered that these alleles, particularly APOE-4 were in most patients determined to have AD, the latter was the most frequent, found in eighty percent of individuals with familial diagnoses and sixty-four percent of those without familial ties. Furthermore, the examination established a higher number of alleles found in an individual, notably with APOE-4, the earlier age-at-onset was, with a mean of 75.5 years of age for a single allele and 68.7 for two alleles. Due to this study, it is accepted that APOE is one of the most common genes associated with the development of Alzheimer’s whether it is inherited or not, meaning further inspections will focus on genes besides APOE. 

A present-date study on the heterogeneity of LOAD, fixated on identifying if there were other biological pathways AD follows apart from the APOE gene. If Milind, Nikhil et al were to discover other pathways, it could help classify genes otherwise unknown to be associated with AD. Taking a section of the brain from deceased elderly with normal to mild cognitive impairment as well as those with other forms of dementia (group A) and juxtaposed data collected to information accumulated from brain sections of those with LOAD (group B). Material from other experiments were included to determine the variation and heterogeneity of AD.  It was determined that there were genetic overlap within the two groups, and heterogeneity in the inflammatory response linked with LOAD displays specific pathways Alzheimer’s follows, thus genes associated with those areas must be connected with the development. 

Joining the aforementioned investigations, a study had scientists looking into the age-at-onset (AAO) how it correlated with AD. Zhao, Wei et al wanted to test for any other ones that contribute to LOAD, besides the two already identified, APP and APOE. They began by collecting genetic data of families with a history of LOAD from multiple universities around the county, including the University of Washington and the Oregon Health Sciences University, and the National Cell Repository for Alzheimer’s Disease. Since is was entire families information, individuals were labeled as affected, unaffected and unknown. The genetic data was then compared, while sorting for AAO and lack of mutation, for any genes that are shared. After multiple tests, there was evidence for linkage of loci AAO on multiple chromosomes, the strongest being 1, 6 and 19 ( Zhao, Wei et al ). This means the genes mostly to be associated with the development of late-onset Alzheimer’s disease will be on these specific chromosomes, thus the scope of genes has been reduced considerably. 

None of these studies have been able to identify specific genes linked with Alzheimer’s Disease, but they have provided a backbone for the studies that will. By singling out those chromosomes and specific pathways, identifying those genes thus better treatments and hopefully a cure is that much closer. More studies and testing are in progress, building on the work of these results, and continuing the research into how this disease works. The information found may even be able to be applied to other forms of dementia or even other hereditary diseases.