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Raffaele Cacciaglia1,2,3, Armand González Escalante1,3, Paula Ortiz-Romero1,3

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Summary

Plasma phosphorylated tau (p-tau217) predicts gray matter atrophy and memory decline in cognitively unimpaired individuals. Elevated glial fibrillary acidic protein (GFAP) amplifies p-tau217

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Area of Science:

  • Neuroscience
  • Biomarker Research
  • Alzheimer's Disease Research

Background:

  • Plasma phosphorylated tau at threonine 217 (p-tau217) is a key Alzheimer's biomarker.
  • p-tau217 and glial fibrillary acidic protein (GFAP) may predict cognitive decline years before symptoms.
  • Impact on brain structure and cognition in unimpaired individuals is not fully understood.

Purpose of the Study:

  • To investigate the association of plasma p-tau217 with gray matter volume (GMV) atrophy and episodic memory (EM) decline in cognitively unimpaired (CU) individuals.
  • To explore the interaction between plasma p-tau217 and GFAP in predicting neurodegeneration and cognitive changes.
  • To assess the predictive value of plasma p-tau217 for preclinical Alzheimer's pathology.

Main Methods:

  • 329 CU individuals from the ALFA+ study with baseline biomarkers, MRI, and cognitive data were analyzed.
  • Longitudinal changes in GMV and EM decline (FCSRT) were assessed over a mean follow-up of 3.35 years.
  • Plasma p-tau217, GFAP, NfL, and Ab42/40 were quantified; brain atrophy measured using SPM; EM decline modeled using linear mixed-effects models.

Main Results:

  • Elevated baseline plasma p-tau217 correlated with GMV atrophy in the hippocampus and temporal lobes.
  • A significant interaction showed that high GFAP amplified GMV loss in the presence of elevated p-tau217.
  • Plasma p-tau217 predicted episodic memory decline, but no interaction with GFAP was found for cognitive decline.

Conclusions:

  • Plasma p-tau217 is linked to neurodegeneration and cognitive decline in CU individuals.
  • The p-tau217 and GFAP interaction suggests early astroglial involvement in neurodegeneration.
  • Plasma p-tau217 is valuable for diagnosing and stratifying high-risk individuals in preclinical Alzheimer's.