Alzheimer disease (AD) is characterized by the accumulation of amyloid b (Ab) and tau aggregates in the brain. The progression of AD can be monitored through imaging techniques or through the use of cerebrospinal fluid (CSF) biomarkers. As these modalities are expensive and invasive, an alternative method is needed. Neurofilament light (NfL) in the CSF is a biomarker for neuroaxonal damage, and recent developments have facilitated measurement of NfL in blood samples. In this cohort study, longitudinal plasma NfL levels were tested in 1,182 patients with mild cognitive impairment or AD dementia to investigate possible associations with other hallmarks of AD, such as CSF Ab and tau, imaging measures, and scores on cognitive tests. At baseline, 855 patients had mild cognitive impairment, and 327 patients had AD dementia. The analysis also included 401 patients who were cognitively unimpaired. Researchers found that the NfL level was increased at baseline in patients with mild cognitive impairment (mean level 37.9 ng/L) and AD dementia (mean level 45.9 ng/L) as compared to those who were cognitively unimpaired (mean level 32.1 ng/L) (p<0.001). Researchers also found that a longitudinal increase in NfL level correlated with baseline CSF biomarkers, including low Aβ42 (p=0.001), high total tau (p=0.02), and high phosphorylated tau levels (p=0.02). A longitudinal increase in NfL level also correlated with magnetic resonance imaging measures (small hippocampal volumes (p<0.001), thin regional cortices (p=0.009), and large ventricular volumes (p=0.002), low fluorodeoxyglucose positron emission tomography uptake (p=0.01), and poor cognitive performance (p< 0.001). A faster increase in NfL levels was also associated with a faster increase in CSF biomarkers of neuronal injury, faster rates of atrophy and hypometabolism, and faster worsening of global cognition. Overall, these findings suggest that plasma NfL levels can be used to track neurodegeneration and disease complications in AD.
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