In Alzheimer’s, a build-up of plaque and dysfunctional proteins in the brain are known to be hallmarks of the disease. While the majority of Alzheimer’s research has focused on accumulation of the protein amyloid beta, researchers have begun to pay closer attention to another protein, tau. Tau has long associated with the disease, however, it hasn’t been studied as thoroughly amyloid beta due to the fact effective ways to image it are only just being developed. Now, a study from researchers at Washington University uses a new imaging agent that binds to tau protein to make it visible in positron emission tomography (PET) scans. The team state that their new contrast has shown that measures of tau are better markers of the cognitive decline characteristic of Alzheimer’s than measures of amyloid beta seen in PET scans. The study is published in the journal Science Translational Medicine.
Earlier studies from the team and others has shown that elevated levels of amyloid beta are the earliest markers of developing Alzheimer’s disease. However, in the earliest stages of Alzheimer’s disease, even with amyloid buildup, many patients are cognitively normal, meaning their memory and thought processes are still intact. This suggests that amyloid changes first and then tau, and it’s the combination of both that tips the patient from being asymptomatic to showing mild cognitive impairment; it is unclear as to how the two interact to drive brain cell death. PET imaging of ß-amyloid in patients’ brains has shed light into its role, especially during early stages of the disease. However, elevated tau measured in cerebrospinal fluid has long been a marker of dementia, with this type of data unable to pinpoint which parts of the brain are gathering abnormal proteins. The current study supports models of Alzheimer’s disease where tau pathology closely tracks changes in brain function that are responsible for the onset of early symptoms in Alzheimer’s.
The currents study analyzed PET imaging of tau and ß-amyloid in 10 patients with mild Alzheimer’s disease and 36 healthy adults, using a new tau agent named T807. Results show that compared to amyloid plaques, tau tangles in the temporal lobe more closely correlated with cognitive deficits, as measured by a battery of memory tests. Data findings show that tau deposits in the temporal lobe also strongly associated with tau detected in the patients’ cerebrospinal fluid.
Results show that the findings propose tau as a better predictor, than ß-amyloid, of dementia during Alzheimer’s disease progression. Data findings show that patients can tolerate a certain amount of tau clumped in the hippocampus, however, once it starts spreading into other areas, particularly the lateral temporal and parietal lobes, this appears to be the tipping point for disease progression.
The team surmise that their analysis establishes that the new tau agent is an important tool for understanding the timeline of Alzheimer’s progression and for defining which regions of the brain are involved. They go on to add that with imaging agents for amyloid beta and now tau available, researchers have the tools necessary to assess the effectiveness of investigational therapies against the buildup of both proteins. For the future, the researchers state that their new agent is approved for use in the context of clinical research trials and likely will prove to be important in imaging the brain for other types of disorders that also involve excess tau buildup, including traumatic brain injury.
Source: Washington University in St. Louis
