Cell: Changes in Tau protein in people with Alzheimer's disease with age

November 20, 2020 // -- Research into Alzheimer's disease has long focused on understanding the role of two key proteins, β amyloid and tau.
forms of the tau protein accumulate in the patient's brain tissue, contributing to the worsening of the disease.
in a new study, Dr. Judith Steen and Dr. Hanno Steen show for the first time that the pathological tau protein changes its form over time, which may mean that it will require multiple drugs to target effectively.
(Photo: www.pixabay.com) For years, pharmaceutical companies have had limited success in developing alzheimer's drugs for β amyloid.
recently, drug discovery has shifted to the development of drugs for tau.
the new findings could help with the current development of a drug for tau, as it suggests that the protein may appear as a set of targets in the early stages of the disease and change later in the disease.
lead researcher Judith Steen said: "The tau protein in Alzheimer's disease looks different at every stage.
found that tau underwent a series of chemical modifications in the gradual process associated with the severity of the disease.
shows that we need different diagnoses and treatments for each stage of the disease.
" the study was published in the journal Cell.
Steen lab team studied tau aggregates in two regions of the brain (forehead and angled) in 49 patients with AD and 42 people with Alzheimer's disease or dementia.
they found that the chemical properties of tau proteins in Alzheimer's patients had changed, with several modifications not found on normal tau proteins, called post-translation chemical modifications or PPM.
in addition, the authors found that the specific chemical modification forms of tau were associated with different stages of the symptoms.
with age, tau tangles build up in our brains, even if we don't get sick.
" but these aggregates aren't that rich and don't look like people with severe Alzheimer's disease.
" team revealed PPM of 95 Tau proteins.
a third of them had not been described before.
team's findings have a direct impact on the treatment of Alzheimer's disease.
"It is likely that multiple antibodies or small molecules will be used to effectively target and remove the tau protein," Steen explains.
team hopes that exploring some of these key chemical modifications could help explain the development and progress of Alzheimer's disease and further reveal the chemical properties of the tau protein in its early stages.
() Source: Tau protein changes correlate with Alzheimer's disease dementia stage Original source: Hendrik Wesseling et al, Tau PTM Profiles Identify Patient Heterogenity and Stages of Alzheimer's Disease Cell, (2020).DOI: 10.1016/j.cell.2020.10.029