By Ana Espino | Published on september 21, 2025 | 3 min read
#Alzheimer #Tau #Neurology
Alzheimer’s disease is a
progressive
neurodegenerative disorder, responsible for
irreversible cognitive decline and
loss of autonomy, associated with the abnormal accumulation of
beta-amyloid and
phosphorylated tau in the brain. It is the
leading cause of dementia worldwide.
Diagnosis still relies heavily on invasive and costly tools: cerebrospinal
fluid (CSF) biomarkers, brain imaging (amyloid or tau PET), and complex
clinical assessments, which are often difficult to access in everyday practice.
These limitations hinder early screening and the implementation of targeted
therapeutic strategies, particularly in the silent stages of the disease.
In this context, a
major challenge
lies in the identification and development of
reliable peripheral biomarkers,
capable of
detecting Alzheimer’s from its earliest stages, distinguishing it
from other causes of dementia, and being easily integrated into primary care.
This review was therefore conducted
to explore the diagnostic potential of blood-based phosphorylated tau markers
(p-tau181, p-tau217, p-tau231), by analyzing their accuracy, their
correlation
with central biomarkers, and their
clinical applicability on a large scale.
Can plasma tau really make the
distinction?
This review is based on a critical analysis of longitudinal and cross-sectional
clinical studies, conducted on cohorts of patients with Alzheimer’s,
individuals with mild cognitive impairment (MCI), and healthy controls. Plasma
concentrations of phosphorylated tau (p-tau181, p-tau217, p-tau231) were
systematically compared with CSF biomarkers, amyloid and tau PET imaging, and
clinical cognitive performance, in order to assess their discriminant value,
biological correlation, and diagnostic relevance.
The results show that blood
p-tau181
and p-tau217 can
effectively distinguish Alzheimer’s patients from controls,
with diagnostic performance comparable to that of CSF (AUC > 0.88 in several
studies). p-tau231 appears to be particularly sensitive to early changes, even
preceding alterations detected by imaging. Moreover, plasma p-tau
concentrations are correlated with cognitive decline, amyloid and tau brain
burden, and the age of symptom onset. These markers are also able to
differentiate Alzheimer’s from other neurodegenerative dementias (DLB, FTD),
making them valuable for early differential diagnosis.
Towards a simple, rapid, and
accessible diagnosis
Alzheimer’s disease remains the leading cause of dementia, characterized by the
accumulation of beta-amyloid and phosphorylated tau in the brain. Diagnosis
still depends on invasive and poorly accessible examinations, hindering early
detection and access to targeted care.
The aim of this review was to
evaluate the potential of blood-based p-tau biomarkers (p-tau181, p-tau217,
p-tau231) as non-invasive diagnostic tools. The results confirm their strong
discriminant power, their correlation with central biomarkers, and their
ability to identify Alzheimer’s from the earliest stages. These markers
therefore pave the way for simpler, faster, and more equitable care, especially
in primary care or large-scale contexts.
However, limitations remain and
justify further research. It is essential to
standardize assay methods,
validate these markers in more diverse populations, and assess their
feasibility in routine clinical practice. Integrating these data into
algorithms that combine imaging, cognition, and genetics could accelerate the
emergence of
precision medicine in neurodegeneration.
Read next: Single-cell epigenomic rewiring in alzheimer’s disease progression and cognitive resilience
About the author – Ana EspinoPhD in Immunology, specialized in Virology
