Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: Tort-Merino A, Olives J, León M, Peñaloza C, Valech N, Santos-Santos MA, Càmara E, Grönholm-Nyman P, Martinez-Lage P, Fortea J, Molinuevo JL, Sànchez-Valle R, Laine M, Rodríguez-Fornells A, Rami L
Publisher: IOS Press
Publication year: 2019
Journal: Journal of Alzheimer's Disease
Journal acronym: J. Alzheimer´s Dis.
Volume number: 70
Issue number: 1
Start page: 211
End page: 225



We investigated a sample of
cognitively healthy subjects with normal Alzheimer's disease (AD)
cerebrospinal fluid (CSF) biomarker levels to identify the earliest
variables related to longitudinal memory changes.


a new highly demanding learning and memory test (the Ancient Farming
Equipment Test; AFE-T), we aimed to investigate whether a biomarker
related to neurodegeneration (i.e., CSF tau) was associated with
longitudinal memory decline.


cognitively and biologically normal (CBN) subjects underwent MRI,
neuropsychological assessment, and the AFE-T at baseline and 18 months
later. To explore the relationship between cognitive performance and
relevant factors, a linear model was set up. For a secondary analysis
that further explore the effect of tau, the subjects were divided into
CBN-Tau↓ (tau < 228.64 pg/ml; n = 16) and CBN-Tau↑
(tau > 228.64 pg/ml; n = 16). We also performed voxel-based
morphometry (VBM) to identify regions of grey matter volume that would
predict both baseline and longitudinal cognitive performance.


main finding was an association between CSF tau and longitudinal memory
decline measured with AFE-T (B = -0.17, p < 0.05; r = -0.414;
p < 0.01), and further analyses showed different evolvement between
subgroups, with an accelerated decline in individuals with higher tau
(F(1,31) = 8.37; p < 0.01). VBM results suggested that AFE-T
performance is related to grey matter volume in a medial temporal,
middle frontal, and posterior cerebellar network at baseline, and that
there are strategic brain areas driving the longitudinal cognitive


The present findings provide
evidence for structural and biological markers linked to cognitive aging
by highlighting the role of tau, a marker of neurodegeneration, which
can be related with the earliest memory changes in healthy subjects.


Aging, biomarkers, cognition, early detection, memory decline, tau, Voxel-based morphometry

Last updated on 2020-04-04 at 05:05