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

• Published in: Neurobiology of aging Vol. 49; pp. 138 - 144
• Main Authors: Idland, Ane-Victoria, Sala-Llonch, Roser, Borza, Tom, Watne, Leiv Otto, Wyller, Torgeir Bruun, Brækhus, Anne, Zetterberg, Henrik, Blennow, Kaj, Walhovd, Kristine Beate, Fjell, Anders Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017; Elsevier Science
• Subjects: Aged; Aged, 80 and over; Aging - pathology; Atrophy; Axons - pathology; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Cerebrospinal Fluid - cytology; Cerebrospinal Fluid - metabolism; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - pathology; Female; Hippocampal atrophy rate; Hippocampus - pathology; Humans; Intermediate Filaments - metabolism; Intermediate Filaments - pathology; Internal Medicine; Magnetic resonance imaging; Male; Middle Aged; Nerve Degeneration - diagnosis; Nerve Degeneration - pathology; Neurofilament light; Neurology; Neurosciences; Neurovetenskaper; Normal aging; Predictive Value of Tests; Neurofilament light; Hippocampal atrophy rate; Cerebrospinal fluid; Magnetic resonance imaging; Normal aging; magnetic resonance imaging; Alzheimer’s Disease; β-amyloid 1-42; Phosphorylated Tau; Multiple Sclerosis; Apolipoprotein E; NFL; MMSE; P-tau; T-tau; AIC; APOE; GAMM; Akaike Information Criterion; AD; the Mini Mental Status Examination; Aβ42; MS; normal aging; neurofilament light; Mild Cognitive Impairment; SNAP; Generalized Additive Mixed Models; White Matter Hypointensities; MCI; hippocampal atrophy rate; Suspected Non-Alzheimer Pathology; WM-hypointensities; cerebrospinal fluid; Total Tau
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2016.09.012

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 (R2 = 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.