CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults

Abstract

Cerebrospinal fluid (CSF) neurofilament light (NFL) is a marker of axonal degeneration. We tested whether CSF NFL levels predict hippocampal atrophy rate in cognitively healthy older adults independently of the established CSF Alzheimer's disease (AD) biomarkers, β-amyloid 1-42, and phosphorylated tau (P-tau). We included 144 participants in a 2-year longitudinal study with baseline CSF measures and 2 magnetic resonance images. Eighty-eight participants had full data available. A subgroup of 36 participants with very low AD risk was also studied. NFL predicted hippocampal atrophy rate independently of age, β-amyloid 1-42, and P-tau. Including NFL, P-tau, and age in the same model, higher NFL and lower P-tau predicted higher hippocampal atrophy (R = 0.20, NFL: β = -0.34; p = 0.003; P-tau: β = 0.27; p = 0.009). The results were upheld in the participants with very low AD risk. NFL predicted neurodegeneration in older adults with very low AD probability. We suggest that factors previously shown to be important for brain degeneration in mild cognitive impairment may also impact changes in normal aging, demonstrating that NFL is likely to indicate AD-independent, age-expected neurodegeneration.

Plasma neurofilament light chain levels in Alzheimer’s disease

“…In agreement with our findings, previous studies suggested that age was correlated with NFL levels in CSF [4,7,14], which were closely related with NFL levels in blood [3]. However, the mechanisms underlying this age-NFL association were largely unknown.…”

Neurofilament Light in Serum and Cerebrospinal Fluid of Hip Fracture Patients with Delirium

“…This highlights the importance of using matched controls also in delirium research. Comorbidities, such as dementia [48], and greater age [36, 49] in an overall frailer hip fracture population are associated with increased levels of NFL in blood and CSF, as confirmed by us. A stronger correlation between NFL in CSF and blood in the elective patients compared to the hip fracture patients further suggests that extracerebral sources of NFL are of greater importance in measured sNFL in the hip fracture population.…”

“…A total of 172 patients undergoing elective gynecological, orthopedic, or urological surgery in spinal anesthesia, aged 65 years or older in the year of inclusion, were recruited to the COGNORM study from 2012 to 2013 at Oslo University Hospital and Diakonhjemmet Hospital, Oslo, as previously described [36]. Participants were evaluated with a multidomain battery of cognitive tests prior to surgery.…”

Delirium and Alzheimer disease: A proposed model for shared pathophysiology

“…Neurofilament light (NfL) is an intermediate filament protein that is expressed in neurons and believed to function primarily to provide structural support for the axon. 43 NfL is a general marker of neuronal injury and neurodegeneration and has also been detected in CSF and blood in multiple conditions including stroke, traumatic brain injury, multiple sclerosis, progressive supranuclear palsy, and frontotemporal dementia. In AD, serum NfL has been shown to be increased in AD and MCI patients compared with controls, with the highest serum levels in cases with positive amyloid PET scans.…”