Scientists have long been trying to find a cure for Alzheimer’s and one of the primary points of research is mouse model. However in case of Alzheimer’s disease research, mouse model hasn’t been too helpful for the disease develops over many years – even decades in some cases – and because mice don’t live that long, studies based on mouse model haven’t been yielding the desired results.
However, that changes with a new research wherein scientists have developed a mouse model that mimics the development of Alzheimer’s disease in humans. Published in the journal Nature Communications, the research was carried out by Johns Hopkins researchers who claim that they garnered greater insights into the disease – specifically, they have found out a one-two punch of major biological “insults” that must occur in the brain to cause the dementia that is the hallmark of the disease.
Scientists have long been aware that Alzheimer’s disease is associated with the accumulation of so-called neurofibrillary tangles, consisting of abnormal clumps of a protein called tau inside brain nerve cells, and by neuritic plaques, or deposits of a protein called beta-amyloid outside these cells along with dying nerve cells, in brain tissue. The tau is known to bunch up inside the nerve cells and beta-amyloid clumps up outside these cells and this combination effectively mucks up the nerve cells controlling memory.
While this was something that was known, researchers haven’t been able to figure out the relationship between the two clumping processes, since one is inside cells and one is outside cells. Prior studies of early-onset Alzheimer’s disease have suggested that the abnormal accumulation of beta-amyloid in the brain somehow triggers the aggregation of tau leading directly to dementia and brain cell degeneration. But authors of the latest study say that the accumulation of beta-amyloid in and of itself is insufficient to trigger the conversion of tau from a normal to abnormal state. Instead, their studies show, it may set off a chain of chemical signaling events that lead to the “conversion” of tau to a clumping state and subsequent development of symptoms.
The base for the claim
As mentioned earlier, the Alzheimer’s disease develops over many years and specifically speaking the lag between development of the beta-amyloid plaques and the tau tangles inside brain nerve cells can be 10 to 15 years or more. But, the lifetime of a mouse is only two to three years, and because of this current animal models that successfully mimic the appearance of beta-amyloid plaques did not offer enough time to observe the changes in tau.
To find a resolution to this problem, Johns Hopkins researchers genetically engineered a mouse model that used a tau fragment to promote the clumping of normal tau protein. They then cross-bred these mice with mice engineered to accumulate beta-amyloid. The result was a mouse model that developed dementia in a manner more similar to what happens in humans.
The researchers found during brain dissections of the animals that the presence of beta-amyloid plaque alone was not sufficient to cause the biochemical conversion of tau, the repeat domain of tau — the part of tau protein that is responsible for the conversion of normal tau to an abnormal state — alone was insufficient for the conversion of tau, beta-amyloid plaques must be present in the brain for the conversion of tau and the tau fragments could “seed” the plaque-dependent pathological conversion of tau.