Alz Res Therapy: cerebrospinal fluid tau protein, helping cognitive function grouping

Abnormal levels of amyloid β1-42 (Aβ42), total tau (tau), and tau phosphorylated at threonine 181 (p-tau-181) are organisms with Alzheimer's disease (AD) pathology in the brain Markers are also part of the established research standards for AD in the entire cognitive continuity
.

The classification scheme based on biomarkers depends on the cut point, and there are different methods to determine this cut point
.

The most commonly used traditional method is to determine the cut point by optimizing the sensitivity and specificity of clinical AD dementia, compared with the control group

For example, nearly 30% of cognitively complete people in their 70s have AD pathology, and up to 20% of clinical AD dementia cases show no AD pathology in neuropathological examinations
.

Therefore, cut points based on clinical labels may be biased

High t-tau levels in cerebrospinal fluid (CSF) are thought to reflect neuronal degeneration or damage.
In various situations involving neuronal death, such as acute stroke, high t-tau levels can be found in CSF
.

In contrast, p-tau-181 is thought to reflect the formation of phosphorylated tau in the brain, and more specifically represents the formation of neurofibrillary tangles, which is one of the neuropathological features of AD
.

Since tau pathology is a sign of AD, it can be assumed that similar to amyloid, t and p-tau levels may be a mixture of normal and affected individuals, from which unbiased cutting points can be determined

In this way, Flora H.
Duits and others of the University of Amsterdam explored the use of Gaussian mixture models to determine the subgroups of CSF t- and p-tau levels and determine the cut-off point
.

They describe the characteristics of the tau subgroup in terms of clinical and biological characteristics and longitudinal trajectories of cognitive decline

They used the Gaussian mixture model in two independent cohorts (the Amsterdam Alzheimer's Cohort and ADNI) to study the entire clinical range of CSF t-tau and p-tau cut points
.

Individuals with normal cognition (NC) (total number=1111), mild cognitive impairment (MCI) (total number=1213), and 6++ t-tau disease dementia (AD) (total number=1524) were included
.

t-tau

In these two cohorts, four CSF t- and p-tau distributions and three corresponding cut-off points were determined
.

The higher and higher tau subgroup is characterized by a faster decline in MMSE and a higher risk of developing AD (cohort/platform dependent HR, t-tau 1.
9-21.
3; p-tau 2.
2-9.
5)
.

The higher and higher tau subgroup is characterized by a faster decline in MMSE and a higher risk of developing AD

The significance of this study is that it found that in two independent cohorts, t-tau and p-tau levels showed four subgroups
.

Higher and higher tau subgroups are associated with faster clinical decline, indicating that this method may contribute to a more precise prognosis

Four subgroups based on tau levels in Alzheimer's disease observed in two independent cohorts.
Alz Res Therapy.

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