Alzheimer's disease: two good news
A new innate protection factor against Alzheimer's disease has been discovered
The genetic change causes suppression of the formation of beta-amyloid, a protein whose fragments accumulate in the brain in the form of plaques characteristic of the disease. Experts consider this discovery interesting, but not particularly unexpected, since it fits perfectly into existing ideas about the nature of Alzheimer's disease.
The new mutation concerns a gene called ARP, which encodes a protein that splits into two parts, one of them is beta-amyloid.
A group of researchers led by neuroscientist Kari Stefansson from the world-famous company deCODE genetics based in Reykjavik, Iceland, having the genome-wide data of 1,795 Icelanders, scanned them for variations in the ARP gene that protect against Alzheimer's disease. Thus, one variant of a single nucleotide substitution was discovered, which scientists paid special attention to. The probability of developing the disease in people over 85 carrying this mutation was, according to geneticists, seven and a half times less than in those who did not have it.
In additional experiments with cell culture in vitro, it was found that the mutation interferes with the work of one of the enzymes that cleave the APP protein, which reduces the level of beta-amyloid production by almost 40 percent.
The results obtained by Stephanson and co-authors are published by Nature (Jonsson et al., A mutation in APP protects against Alzheimer's disease and age–related cognitive decline - VM).
Earlier, scientists discovered more than 30 mutations in the ARP gene, but none of them gave a satisfactory effect. Some genetic changes, on the contrary, increased the production of beta-amyloid and were associated with a severe hereditary form of Alzheimer's disease, which affects people aged 30-40 years, that is, much earlier than the usual development of the disease in 70-80-year-olds.
Before the discovery of Icelandic scientists, another variant of natural genetic protection against Alzheimer's disease was known, the so-called AROE2 allele. However, according to Stefanson, the new variant of the gene, although less common, protects more effectively. It not only provides a low level of beta-amyloid formation, but also protects against memory impairment and other cognitive impairments. After examining thousands of people living in nursing homes across Iceland, scientists found that carriers of a rare mutation in their 80s and 90s are much better at coping with mental tasks than their non-mutant peers.
The amyloid hypothesis of the nature of Alzheimer's disease, which implies the accumulation of beta-amyloid fragments as the main cause of the disease, has recently been challenged by the results of clinical trials that showed the ineffectiveness of drugs aimed at reducing the production of this protein in the brain. However, experts now see the reason for this in the belated beginning of the tests themselves, when the violations became irreversible.
An international study (Bateman et al., Clinical and Biomarker Changes in Predominantly Inherited Alzheimer's Disease, freely available – VM), which was published in the latest issue of the New England Journal of Medicine, presents a timeline for predicting the development of Alzheimer's disease in people with a genetic risk of developing this disease. According to this scale, the first signs of beta-amyloid accumulation are detected in the cerebrospinal fluid 25 years before the onset of the disease, the level of another key factor of neurodegenerative diseases, tau protein, increases in 15 years, the level of glucose metabolism in the brain changes 10 years before the first symptoms, and some memory problems begin.
Portal "Eternal youth" http://vechnayamolodost.ru13.07.2012