New biomarkers for early diagnosis of Alzheimer's disease

Until recently, a final diagnosis of Alzheimer's (AD) used to be only possible
after someone died.
However, contemporary biomarker research has led to the development of
imaging and spinal fluid detection.
These tests can only monitor severe disease, distinguishing advanced AD from related diseases
.
Scientists have now identified a biomarker that could help doctors diagnose AD
earlier when patients transition to mild cognitive impairment (MCI).
The findings were published
today (November 9) in the journal Chemical Neuroscience of the ACS.

In their search for biomarkers for AD, some researchers turned to the study
of subtle changes in a protein called tau.
These changes, or post-translational modifications, make tau proteins more likely to aggregate, leading to neuronal loss and impaired
memory.

Two of these modifications involve phosphorylation of tau proteins on specific amino acids, resulting in versions
known as p-tau181 and p-tau217.
These biomarkers have been shown to be effective in distinguishing AD tissue from tissues from those of patients with other neurodegenerative diseases
.
Because it is helpful to have many biomarkers in a doctor's toolbox, Bin Xu, Jerry Wang, Ling Wu and colleagues looked for more p-tau biomarkers that could be valid for AD diagnosis or could be detected
in the early stages of AD.

Using postmortem brain tissue from AD patients and non-AD subjects, the researchers identified several p-tau biomarkers associated with selectivity for tau protein aggregation
.
Like p-tau181 and p-tau217, these biomarkers distinguish AD tissue from healthy controls
.
One of them — p-tau198 — also distinguishes
AD from two other neurodegenerative diseases in which tau protein aggregation is known.

Further experiments showed that p-tau198 was equally effective
with p-tau181 and p-tau217 in these trials.
Importantly, p-tau 198 and p-tau217 can also distinguish brain tissue from older subjects without damage in patients with MCI (early symptoms of AD
).

According to the researchers, there are currently no well-established biomarkers that can diagnose mild cognitive impairment
.
Therefore, p-tau198 and p-tau217 can help clinicians intervene early as
new therapies become available before major neurological damage occurs.
In addition, the researchers say, this method could be used to look for tau biomarkers with modifications other than phosphorylation
.

Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation