Tau defects on PET emerge as prime predictors of early-onset Alzheimer’s

Younger Alzheimer’s patients have disproportionately more tau pathology on PET-CT imaging than older patients who are similarly symptomatic, according to a small multicenter European study. The authors suggest defective tau proteins alone can predict disease onset and progression, while later-developing Alzheimer’s likely owes to a confluence of contributing factors.

The team has published its findings online in the Journal of Alzheimer’s Disease.

Ivan Koychev, PhD, of the University of Oxford and colleagues recruited 22 participants ranging in age from 50 to 85 who had previously been diagnosed with early-stage Alzheimer’s.

They examined the patients with cognitive assessments plus measurements of cerebrospinal fluid, recording amyloid beta and tau at baseline and six months.

They imaged amyloid beta using PET-CT with Florbetapir (18F). They imaged tau with PET-CT with 18F-AV-1451 (also known as T807).

Analyzing the PET biomarkers, the researchers found a strong negative correlation between age and tau in multiple regions.

Specifically, entorhinal cortex tau and age interacted significantly in terms of cognitive change over six months. This may have owed to older participants deteriorating faster despite lower levels of cortical tau, the authors point out.

Further, cortical amyloid beta associated with entorhinal cortex tau, while cerebrospinal fluid tau/amyloid beta ratio correlated strongly with cortical tau but not with amyloid beta.

“The negative relationship between age and cortical tau whereby younger patients with mild Alzheimer’s disease had relatively greater tau burden is potentially important,” the authors conclude. “It suggests that younger-age onset Alzheimer’s disease may be primarily driven by tau pathology, while Alzheimer’s disease developing later may depend on a multitude of pathological mechanisms.”

Koychev et al. state their data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated Alzheimer’s diagnostic marker: cerebrospinal fluid total tau/amyloid beta ratio.

The journal has posted the study in full for free.