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

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 tau(231) (p-tau(231)), total tau, the amyloid beta (A beta) A beta 42/A beta 40, t-tau/A beta 42 and p-tau(231)/A beta 42 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-tau(231) (Z = -2.2, p = 0.03), lower A beta 42/A beta 40 (t = -2.2 [55], p = 0.04) and greater longitudinal MTL GM reductions (t([52]) = -2.70, p = 0.01). Higher baseline p-tau(231) was also associated with the absolute decrease in memory scores (rho = -0.30, p = 0.02) and with longitudinal MTL GM reduction (F-[2,F-52] = 4.4, p = 0.04, age corrected). Our results indicate that in normal individuals, elevated p-tau(231), 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. (C) 2010 Elsevier Inc. All rights reserved.