CSF Aβ42 and tau biomarkers in cognitively unimpaired Aβ- middle-aged and older APOE ε4 carriers

Yen Ying Lim, Nawaf Yassi, Lisa Bransby, Scott Ayton, Rachel F. Buckley, Dhamidhu Eratne, Dennis Velakoulis, Qiao Xin Li, Christopher Fowler, Colin L. Masters, Paul Maruff

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4 Citations (Scopus)

Abstract

This study aimed to determine the relationship between the apolipoprotein E (APOE) ε4 allele and cerebrospinal fluid (CSF) and neuroimaging biomarkers of Alzheimer's disease, and cognition in cognitively unimpaired (CU) middle-aged adults (n = 82; Mage = 58.2), and in Aβ- CU older adults (n = 71; Mage = 71.8). Aβ- CU middle-aged ε4 carriers showed lower CSF Aβ42 levels, higher levels of CSF total tau (t-tau) and neurofilament light (NfL), and poorer cognitive performance compared to noncarriers (Cohen's d: 0.30–0.56). In Aβ- CU older adults, ε4 carriers also had lower CSF Aβ42 levels and higher levels of CSF t-tau and p-tau181, compared to noncarriers (Cohen's d: 0.65–0.74). In both Aβ- middle-aged and older adults, hippocampal and total brain volume were equivalent between ε4 carriers and noncarriers. In Aβ- CU middle-aged adults, APOE ε4 is associated with decreased levels of Aβ, increased tau and NfL, and poorer cognition. Similar relationships were observed in Aβ- CU older adults. These results have implications for understanding clinicopathological relationships between APOE ε4 and the emergence of cognitive and biomarker abnormalities in Aβ- adults.

Original languageEnglish
Pages (from-to)209-218
Number of pages10
JournalNeurobiology of Aging
Volume129
DOIs
Publication statusPublished - Sept 2023

Keywords

  • Alzheimer's disease
  • Amyloid
  • Apolipoprotein E
  • Cognition
  • Phosphorylated tau

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