Phosphorylated tau 231, memory decline and medial temporal atrophy in normal elders

Abstract 

Little is known whether cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) can predict both memory decline and associated longitudinal medial temporal lobe (MTL) gray matter (GM) reductions in cognitively healthy individuals. Fifty-seven normal elderly subjects received comprehensive evaluation at baseline and 2 years later. The baseline phosphorylated tau₂₃₁ (p-tau₂₃₁), total tau, the amyloid beta (Aβ) Aβ42/Aβ40, t-tau/Aβ42 and p-tau₂₃₁/Aβ42 ratios were examined as predictors of memory change and reductions in the global and MTL GM, determined from T1-weighted MRI. Twenty out of 57 participants experienced reduced memory performance at follow-up. The group with decreased memory performance showed higher baseline p-tau₂₃₁ (Z=−2.2, p=0.03), lower Aβ42/Aβ40 (t=−2.2 [55], p=0.04) and greater longitudinal MTL GM reductions (t_[52]=−2.70, p=0.01). Higher baseline p-tau₂₃₁ was also associated with the absolute decrease in memory scores (rho=−0.30, p=0.02) and with longitudinal MTL GM reduction (F_[2,52]=4.4, p=0.04, age corrected). Our results indicate that in normal individuals, elevated p-tau₂₃₁, a marker of neurofibrillary pathology is related to both a decrease in declarative memory and progressive atrophy of the MTL, suggesting its diagnostic potential in preclinical stage.

Keywords: Alzheimer's disease, Aging, Memory performance, Prediction, Biomarkers, Phosphorylated tau 231, Cerebrospinal fluid, Medial temporal lobe