Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease

• Published in: Neurobiology of aging Vol. 79; pp. 131 - 141
• Main Authors: Timmers, Maarten, Tesseur, Ina, Bogert, Jennifer, Zetterberg, Henrik, Blennow, Kaj, Börjesson-Hanson, Anne, Baquero, Miquel, Boada, Mercè, Randolph, Christopher, Tritsmans, Luc, Van Nueten, Luc, Engelborghs, Sebastiaan, Streffer, Johannes Rolf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2019
• Subjects: Aged; Alzheimer Disease - diagnosis; Alzheimer Disease - psychology; Alzheimer’s disease; Amyloid; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers - cerebrospinal fluid; Cognition; Cross-Sectional Studies; Female; Humans; Interaction; Male; Medicin och hälsovetenskap; Middle Aged; Neuropsychological Tests; Neurosciences; Neurovetenskaper; Peptide Fragments - cerebrospinal fluid; RBANS; Tau; tau Proteins - cerebrospinal fluid; Tau; Amyloid; Cognition; Alzheimer’s disease; RBANS; Interaction
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.03.016

Amyloid β (Aβ) and tau are key hallmark features of Alzheimer's disease (AD) neuropathology. The interplay of Aβ and tau for cognitive impairment in early AD was examined with cross-sectional analysis, measured by cerebrospinal fluid biomarkers (Aβ1–42, total tau [t-tau], and phosphorylated tau [p-tau181P]), and on cognitive performance by the repeatable battery for assessment of neuropsychological status (RBANS). Participants (n = 246) included cognitively normal (Aβ−), mild cognitively impaired (Aβ−), preclinical AD (Aβ+), and prodromal AD (Aβ+). Overall, cognitive scores (RBANS total scale score) had a moderate negative correlation to t-tau (n = 246; r = −0.434; p < 0.001) and p-tau181P (r = −0.389; p < 0.001). When classified by Aβ status, this correlation to t-tau was applicable only in Aβ+ participants (n = 139; r = −0.451, p < 0.001) but not Aβ− participants (n = 107; r = 0.137, p = 0.16), with identical findings for p-tau. Both tau (p < 0.0001) and interaction of Aβ1–42 with tau (p = 0.006) affected RBANS, but not Aβ1–42 alone. Cognitive/memory performance correlated well with cerebrospinal fluid tau levels across early stages of AD, although the correlation is Aβ dependent. •Amyloid-β and tau interplay is implicated in the early Alzheimer's disease (AD) continuum.•A negative correlation between CSF tau levels and cognitive scores was observed in the early AD continuum, although the negative correlation is Aβ dependent (only present if CSF Aβ < 600 ng/mL).•Both CSF tau and the interaction of CSF Aβ1–42 with CSF tau were significant in their negative effect on cognitive scores but not Aβ1–42 alone.