In two new studies, researchers have found new forms of tau protein that become abnormal in the very early stages of Alzheimer’s disease before cognitive problems develop.
They developed new tools to detect these subtle changes and confirmed their results in human samples.
At a time when the incidence and social costs of dementia and Alzheimer’s disease, in particular, continue to rise, this breakthrough is very timely as it could enable the detection of the disease much earlier than current approaches.
The findings are also important for the testing of therapies against this devastating disease.
The research was conducted by a team at the University of Gothenburg in Sweden and elsewhere.
Alzheimer’s disease is characterized by two pathological changes in brain tissue. One is a protein called tau while the other involves the amyloid beta-peptide.
Both can form clumps of aggregates that progressively accumulate in specific areas of the brain.
For tau, individual units of the protein can aggregate into finely-ordered fibrillar structures facilitated by a biochemical process called phosphorylation.
Throughout the disease process, amyloid beta and phosphorylated tau (p-tau) is released from the brain into the cerebrospinal fluid; the amount of the released proteins are used as reliable surrogate markers for clinical diagnoses of Alzheimer’s disease.
Normally, amyloid-beta levels in the cerebrospinal fluid become abnormal several years before p-tau. The current clinical tests for p-tau become abnormal when memory failings develop.
This makes it difficult to identify people with the disease at the very early stages before it is too late.
In the study, the team discovered that there are specific forms of p-tau that undergo very minute increases in cerebrospinal fluid and blood in people with emerging Alzheimer’s pathology.
Consequently, the researchers developed highly sensitive techniques to measure these biological markers that precede clinical signs by several years.
At the Barcelona Beta Research Centre (BBRC), the team used the new method found that about a third of the 381 people ad brain evidence of Alzheimer’s pathology but without any cognitive problems.
This means that these changes could not be detected in the clinic by memory assessments.
Remarkably, the new p-tau markers correctly identified these emerging abnormalities measured in cerebrospinal fluid and regular blood samples.
Subsequent tests performed in Gothenburg, Paris, and Ljubljana revealed that these new markers continue to increase from the preclinical stage through the onset of cognitive problems to the late dementia stages.
For this reason, progressive increases in p-tau could provide insights into the biological and clinical development of Alzheimer’s disease.
According to the team, the biomarker detected in the blood may change clinical practice in the coming years, since it will improve the diagnosis of patients with Alzheimer’s disease, both in its asymptomatic and symptomatic phases.
One author of the study is Kaj Blennow, professor of neurochemistry at the University of Gothenburg.
The study is published in EMBO Molecular Medicine and Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Copyright © 2020 Knowridge Science Report. All rights reserved.
