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Serum neurofilament light chain in healthy elderly and in patients with age‐related macular degeneration

2019; Wiley; Volume: 98; Issue: 3 Linguagem: Inglês

10.1111/aos.14270

1755-3768

Marie Krogh Nielsen, Yousif Subhi, Christopher Rue Molbech, Finn Sellebjerg, Torben Lykke Sørensen,

Alzheimer's disease research and treatments

Age-related macular degeneration (AMD) is a prevalent disease with progressive loss of neuroretina. Age-related macular degeneration (AMD) holds similarities with other complex neurodegenerative diseases, such as Alzheimer's, strongly illustrated by (1) involvement of progressive dysregulation and deterioration of multiple signalling pathways, (2) temporal accumulation of proinflammatory lesions, (3) insidious inflammatory neurodegeneration leading to neural cell atrophy and death and to progressive loss of function. The retinal pigment epithelium (RPE) being of neuroectodermal origin, it is more similar to neurons than any other epithelium (Simó et al. 2010). Thus, it may be plausible that mechanisms of cell death in brain neurons are comparable to RPE dysfunction in AMD. Neurofilament light chain (NfL) is an axonal cytoskeleton component considered as a blood biomarker for the presymptomatic phase of Alzheimers’ disease (Preische et al. 2019). There is a strong association between NfL from blood serum and cerebrospinal fluid, making it more usable since individuals do not need to undergo lumbar puncture (Bacioglu et al. 2016). We hypothesized that an immunological neurodegenerative drive could be present in late AMD and that this neurodegenerative drive would be reflected in NfL levels since this test is sensitive to even low levels of neurodegeneration. This case–control study was approved by the Regional Ethics Committee (jr.no. SJ-385) and adhered to the Declaration of Helsinki. Oral and written-informed consent was obtained from participants. Since participants were also included for a study on immunological alterations (Subhi et al. 2017; Krogh Nielsen et al. 2019), individuals with any cancer, ongoing infectious or inflammatory diseases were not included. We excluded participants with any known neurodegenerative disease, dementia, neuropathy, diabetes or excessive alcohol use (above 14 units per week), to avoid confounding from other neurodegenerative processes. The diagnostic approach is described in more detail in Krogh Nielsen et al. (2019). For this study, we included 179 eligible participants: 67 healthy controls, 51 with geographic atrophy and 61 with neovascular AMD. Across groups, participants differed in age (participants with GA were significantly older than the other groups, p < 0.001), but not gender, body mass index, physical activity, smoking habits or co-morbidities (p > 0.05 for all). We measured NfL in serum using a single molecule array immunoassay (NF-Light Advantage Kit and SR-X instrument, both from Quanterix, Billerica, MA, USA). All samples were run in duplicate and blinded from clinical or demographic information. We found that NfL increases significantly as a function of age in individuals above the age of 60, regardless of diagnosis being neovascular AMD (slope = 0.87; 95% CI = 0.48–1.26; p < 0.001), geographic atrophy (slope = 1.06; 95% CI = 0.37–1.75; p = 0.003), or healthy control individuals (slope = 0.47; 95% CI = 0.22–0.72; p < 0.001; Fig. 1). Multivariable logistic regression analysis, with age and diagnosis as covariates, showed no significant difference in levels of NfL between patients with neovascular AMD and healthy controls (p = 0.27), GA and healthy controls (p = 0.22), or between patients with GA and neovascular AMD (p = 0.81). In conclusion, patients with late AMD do not appear to have higher levels of NfL. However, we found a high proportion of outliers in our sample (Fig. 1). This is of particular importance in planning case–control studies of NfL measures, especially in elderly individuals, where subtle neurodegeneration and cognitive decline may not be uncommon. Measuring of NfL levels in elderly should be accompanied by a thorough characterization of possible subtle neurodegeneration, such as subclinical dementia, which could influence the measures.