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

Abstract

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.