The first predictive blood tests for future risk of Alzheimer’s disease were developed in recent years based on correlations between marker proteins in the blood and disease risk derived from large epidemiological studies. One such marker is phosphorylated tau 217 (p-tau217), a modified variant of the tau protein involved in Alzheimer’s disease pathology. People with higher levels in a blood sample have a greater chance of developing Alzheimer’s disease symptoms in the years ahead, as the mechanisms of neurodegeneration are already operating at a higher than average level in their brain cells. Tau becomes pathological and damaging when it is hyperphosphorylated, aggregating and provoking chronic inflammation in brain tissue.
The medical community is somewhat reluctant to engage with this sort of testing because there is no easy prescription to follow up with. But the interesting question remains: what should one do if a blood test shows a high level of p-tau217? The obvious first answer is to look at all of the lifestyle factors that correlate with risk of Alzheimer’s disease, based on epidemiological studies, and modify one’s lifestyle choices appropriately. More speculatively, get vaccinated, based on the ongoing discussion over the evidence for late life vaccinations of various sorts to reduce the risk of dementia via trained immunity. The same might be said for taking antiviral drugs, based on similar discussions centered on the possible role of persistent viral infections in neurodegenerative conditions. After than, one might look at what else can be done to reduce age-related chronic inflammation, given its prominent role in neurodegenerative conditions, but all such strategies are probably things one should be undertaking regardless.
Prognostic Value of Blood-Based P-Tau217 Levels for Progression to Cognitive Impairment
Blood-based biomarkers have fundamentally transformed Alzheimer disease research and have become a common feature of observational cohorts and prevention trials. Does plasma phosphorylated tau 217 (p-tau217) predict absolute long-term risk of clinical progression in cognitively unimpaired older adults across multiple aging and Alzheimer disease cohorts?
In this pooled multicohort study of 2,684 cognitively unimpaired participants across 6 selected longitudinal studies, higher baseline plasma p-tau217 levels were significantly associated with increased risk of progression to cognitive impairment over up to 13.5 years of follow-up. Individuals with very high p-tau217 levels (more than 2.5 standard deviations above the mean) had an estimated 38% absolute risk of progression over 5 years, with higher risk over 10 years, although longer-horizon estimates were constrained by sparsity of data.
These findings support the potential of p-tau217 for prognostic model development and estimation of long-term risk of cognitive decline among cognitively unimpaired individuals, although further research in unselected and more generalizable populations is needed.
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