Plasma neurofilament light chain as a biomarker of Alzheimer’s disease in Subjective Cognitive Decline and Mild Cognitive Impairment

Abstract

Introduction Neurofilament light chain (NfL) is becoming increasingly notable in neurological diseases including AD, and it has been suggested as a new peripherical biomarker of neurodegeneration. We aimed to compare plasma NfL levels among Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI), and AD patients and to evaluate relationships between NfL and CSF biomarkers and neuropsychological scores. Materials and methods We enrolled 110 patients (34 SCD, 53 MCI, and 23 AD), who underwent clinical and neuropsychological evaluation, APOE genotyping, and plasma NfL analysis. Ninety-one patients underwent at least one amyloid burden biomarker (CSF and/or amyloid PET); 86 patients also underwent CSF phosphorylated-tau (p-tau) and total-tau (t-tau) measurement. Patients were classified as A + if they presented at least one positive amyloid biomarker or A− if not. Results NfL levels were significantly increased in AD and MCI compared to SCD patients. These differences depend on A status, e.g., SCD A + had lower NfLs than MCI A + but comparable with MCI A−. Similarly, MCI A + had higher NfL levels than MCI A−, but comparable with AD. NfL levels correlated with p-tau in SCD, with all CSF biomarkers in MCI patients. No correlations were found in AD subgroup. In SCD, NfL levels were negatively correlated with memory test scores. Conclusions Plasma NfL levels might be a promising biomarker for neurodegeneration to discriminate cognitive decline due to AD from other conditions causing cognitive impairment in prodromal stages. Considering correlations with CSF p-tau and memory tests in SCD, NfL might be a useful peripheral biomarker also in preclinical phases of AD.

Plasma neurofilament light chain predicts Alzheimer's disease in patients with subjective cognitive decline and mild cognitive impairment: A cross‐sectional and longitudinal study

“…It should be noted that patients with isolated Aβ biomarker positivity had the same NfL levels at baseline and showed the same change of NfL over years as patients with normal AD biomarkers, in line with previous reports [15, 16, 26] and with the hypothesis raised by Benedet et al [30] that NfL concentration increases when Aβ pathology and tauopathy are associated. This evidence may have a relevant clinical implication in terms of the risk of AD and progression to dementia.…”

“…Notably, the concentration of NfL in SCD and MCI patients within the ATN+ group did not differ from patients with dementia due to AD. This suggests that these differences between SCD, MCI and AD were not driven by cognitive levels but rather by the underlying pathological substrate, as proposed by Giacomucci et al [26]. This finding is particularly interesting for SCD patients and is in line with longitudinal studies showing that blood NfL levels increase more than a decade before the onset of clinical manifestations in carriers of amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) mutations [17].…”

Predicting amyloid PET positivity using plasma p‐tau181 and other blood‐based biomarkers

“…After adjusting age and sex, NfL evidenced a moderate value in discriminating Aβ status (AUC = 0.687). Some previous reports have shown the possibility of using plasma NfL to discriminate Aβ status 36 . The NfL levels may potentially improve the performance of other plasma biomarkers that are specific to AD; however, it is important to note that NfL is not an AD‐specific biomarker.…”

Cognitive and biological effects of citrus phytochemicals in subjective cognitive decline: a 36-week, randomized, placebo-controlled trial

“…They included levels of brain-derived neurotrophic factor and insulin-like growth factor-1 [ 71 , 72 ], nitric oxide, thiobarbituric acid reactive substances, and superoxide dismutase [ 71 , 73 ], and pro- and anti-inflammatory molecules and cytokines [ 74 , 75 ]. In addition, we included neurofilament light chain because this protein is becoming increasingly valuable as a peripheral biomarker of neuronal damage and subjective cognitive decline [ 76 ].…”