Amyloid biomarker changes correlate with the rapid increase of tau biomarkers within the cerebrospinal fluid (CSF) of individuals with early Alzheimer disease (AD) experiencing mild cognitive symptoms, according to study findings published in Alzheimer’s & Dementia (Amsterdam).
In 2009, researchers at Johns Hopkins in Baltimore, Maryland, resumed a longitudinal study (BIOCARD) that was first conducted at the National Institutes of Health (NIH) between 1995 and 2005 when the study was stopped. They reinitiated CSF collection in 2015. They analyzed changes in CSF biomarkers for AD in 278 adults over a median follow-up time of 10.7 years.
CSF biomarkers included amyloid beta (Aβ)42/Aβ40 ratio, phosphorylated tau181 (p-tau181), and total tau (t-tau), which the researchers studied using automated electrochemiluminescence assays. They also assessed whether apolipoprotein E (APOE) genotypes and biological sex influenced CSF biomarker trajectories.
During the study period, 94 adults (34%) who were middle-aged or in late adulthood progressed from normal cognitive baselines to mild cognitive impairment. Overall, these patients typically were older, had shorter follow-up periods, and exhibited more abnormal CSF biomarkers with greater rates of change, especially in tau increases, prior to onset of cognitive symptoms.
APOE ε4 carriers demonstrated significantly lower Aβ42/Aβ40 ratios compared with noncarriers. All CSF biomarkers changed significantly over time in APOE ε4 carriers with decreasing Aβ42/Aβ40 ratios and increasing p-tau181 and t-tau. After reaching Aβ42/Aβ40 positivity, individuals with an APOE ε4 genotype demonstrated greater increases in tau.
Researchers also observed a significant association between age and time for Aβ42/Aβ40 and t-tau biomarkers, while age factors alone impacted all 3 biomarkers.
They noted that lower baseline levels of Aβ42/Aβ40 correlated with greater increased in tau, particularly in men. Overall, abnormal CSF biomarkers did not correlate with biological sex or educational level.
“Our results confirm accelerated biomarker changes during preclinical AD and highlight the important role of amyloid levels in tau accelerations,” the researchers noted.
They also acknowledged that “These findings are consistent with hypothetical AD biomarker models, 2 proposing accelerated biomarker changes during preclinical AD, with these changes occurring over long periods of time beginning as early as midlife.”
Study limitations include the inability to generalize results outside of individuals who are White and highly educated with a family history of dementia; lack of statistical power to detect 30way interactions; insufficient methods to adjust for preanalytic factors resulting in underestimation of Aβ42/Aβ40 effects; and limited CSF collections among individuals after they progressed to AD or dementia.
Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
This article originally appeared on Neurology Advisor
Pettigrew C, Soldan A, Wang J, et al. Longitudinal CSF Alzheimer’s disease biomarker changes from middle age to late adulthood. Alzheimers Dement (Amst). Published online November 18, 2022. doi:10.1002/dad2.12374