Alzheimer’s disease, the primary cause of dementia in the elderly, imposes a tremendous social and economic burden on modern society.
In Japan, the burden of the disease in 2050 is estimated to be a half a trillion US dollars, a figure equivalent to the government’s annual revenues.
Unfortunately, it has proven very difficult to develop drugs capable of ameliorating the disease. After a tremendous burst of progress in the 1990s, the pace of discoveries has slowed. Dr. Saido believes that part of the difficulty is the inadequacy of current mouse models to replicate the real conditions of Alzheimer’s disease and allow an understanding of the underlying mechanisms that lead to neurodegeneration. In fact, much of the research in Alzheimer’s disease over the past decade may be flawed, as it was based on unrealistic models.
The problem with older mouse models is that they overexpress a protein called amyloid precursor protein, or APP, which gives rise to the amyloid-beta (Abeta) peptides that accumulate in the brain, eventually leading to the neurodegeneration that characterizes Alzheimer’s disease. However, in mice the overexpression of APP gives rise to effects which are not seen in human Alzheimer’s disease.
For example, the APP mutant mice often die of unknown causes at a young age, and the group believes this may be related to the generation of toxic fragments of APP, such as CTF-beta. In addition, some of the fragments of APP could be neuroprotective, making it difficult to judge whether drugs are being effective due to their effect on Abeta peptides, which are known to be involved in human AD, or whether it is due to other effects that would not be seen in human disease. In addition, the gene for expressing APP is inserted in different places in the genome, and may knock out other genes, creating artifacts that are not seen in humans.
With this awareness, more than a decade ago Dr. Saido launched a project to develop a new mouse model that would allow more accurate evaluation of therapies for the disease. One of the major hurdles involved a part of the gene, intron 16, which they discovered was necessary for creating more specific models.
The first mice model they developed (NL-F/NL-F) was knocked in with two mutations found in human familial Alzheimer’s disease. The mice showed early accumulation of Abeta peptides, and importantly, were found to undergo cognitive dysfunction similar to the progression of AD seen in human patients. A second model, with the addition of a further mutation that had been discovered in a family in Sweden, showed even faster initiation of memory loss.
These new models could help in two major areas. The first model, which expresses high levels of the Abeta peptides, seems to realistically model the human form of AD, and could be used for elucidating the mechanism of Abeta deposition. The second model, which demonstrates AD pathology very early on, could be used to examine factors downstream of Abeta-40 and Abeta-42 deposition, such as tauopathy, which are believed to be involved in the neurodegeneration. These results may eventually contribute to drug development and to the discovery of new biomarkers for Alzheimer’s disease. The group is currently looking at several proteins, using the new models, which have potential to be biomarkers.
According to Dr. Saido, “We have a social responsibility to make Alzheimer’s disease preventable and curable. The generation of appropriate mouse models will be a major breakthrough for understanding the mechanism of the disease, which will lead to the establishment of presymptomatic diagnosis, prevention and treatment of the disease.”
The Latest on: Alzheimer’s
via Google News
The Latest on: Alzheimer’s
- Phoenix lab using artificial intelligence to stop Alzheimer'son January 17, 2020 at 5:15 pm
PHOENIX — A Phoenix laboratory is trying to stop Alzheimer's disease by using artificial intelligence. Arizona has the fastest growing rate of Alzheimer's disease in the country. According to a 2018 ...
- Thank You Congressman Johnson - Alzheimer's Budget Approvalon January 17, 2020 at 3:32 pm
One of your neighbors posted in Neighbor Posts. Click through to read what they have to say. (The views expressed in this post are the author’s own.) ...
- Film fest: 'Our Time Machine' presents rare opportunity for discussion of Alzheimer'son January 17, 2020 at 10:52 am
Film fest: 'Our Time Machine' presents rare opportunity for discussion of Alzheimer's "Our Time Machine' details the journey of Maleonn, who realizes that his father suffers from Alzheimer's disease.
- Hydromethylthionine impacts brain function in patients with Alzheimer’son January 17, 2020 at 5:50 am
Hydromethylthionine, a potent tau aggregation inhibitor, showed pharmacological activity on brain structure and function as both monotherapy and as an add-on to symptomatic treatment in certain ...
- Custom 1974 Ford Bronco Being Auctioned For Alzheimer’s Charityon January 17, 2020 at 2:54 am
Proceeds from the Barrett-Jackson Scottsdale auction will benefit the Alzheimer's Association. Earlier in the year, Speed Digital (Motorious.com's parent company) client Gateway Bronco announced that ...
- Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s diseaseon January 17, 2020 at 2:38 am
In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner.
- Microglia: a new target in the brain for depression, Alzheimer’s, and more?on January 17, 2020 at 1:54 am
When that happens, they can generate too much synaptic pruning, neuroinflammation, and symptoms of cognitive, mood, and behavioral disorders, from depression to Alzheimer’s disease. This revelation, ...
- Study Reveals a New Way That Stress and Aging Lead to Alzheimer’son January 16, 2020 at 10:56 am
Researchers find that a targeted approach being developed to treat certain cancers also appears to help rewire brain circuitry in Alzheimer’s disease. The body is presented with stressors throughout ...
- Possible Missing Link in Alzheimer’s Pathology Identifiedon January 16, 2020 at 8:01 am
Alzheimer's disease has long been characterized by the buildup of two distinct proteins in the brain: first beta-amyloid, which accumulates in clumps, or plaques, and then tau, which forms toxic ...
- 7 rules to reduce your risk of Alzheimer’s and keep your brain healthyon January 16, 2020 at 12:59 am
Research has homed in on seven pillars for living a brain-healthy lifestyle Scientists have found that people who feel lonely or isolated have a 26% increase in dementia and mild cognitive decline.
via Bing News