Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria

Abstract

Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline.

Plasma‐derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms: A community‐based study

“…Three studies conducted both cross‐sectional and longitudinal analyses on the association between neuropsychiatric symptoms and blood‐based biomarkers. A study from Austria showed associations between serum NfL and neuropsychiatric symptoms in cross‐sectional but not longitudinal analyses among 237 AD patients 45 . In contrast, research from the United States failed to establish cross‐sectional associations between plasma levels of Aβ42 or Aβ42/Aβ40 and depression, but low Aβ42/Aβ40 at baseline was associated with an increased risk of developing depression after 9 years of follow‐up in APOE Ɛ4 carriers but not in non‐carriers 24 .…”

“…A study from Austria showed associations between serum NfL and neuropsychiatric symptoms in cross‐sectional but not longitudinal analyses among 237 AD patients. 45 In contrast, research from the United States failed to establish cross‐sectional associations between plasma levels of Aβ42 or Aβ42/Aβ40 and depression, but low Aβ42/Aβ40 at baseline was associated with an increased risk of developing depression after 9 years of follow‐up in APOE Ɛ4 carriers but not in non‐carriers. 24 Furthermore, a population‐based cohort study among 980 older adults revealed conflicting findings—that is, persons with high Aβ40 levels had more clinically relevant depressive symptoms in cross‐sectional analyses at baseline, whereas in longitudinal analyses, persons with low levels of Aβ40 and Aβ42 had a higher risk of developing clinically relevant depressive symptoms over a mean follow‐up of 11 years.…”

Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development

“…Using ultrasensitive single-molecule array assays (Simoa), it is possible to measure low concentrations of NfL, not only in the CSF but also in blood samples, with very high sensitivity. In this prospective study of patients with AD conducted by Kern et al [ 5 ], higher sNfL concentrations were associated with worse cognitive performance, and there were no significant associations with respect to changes in neuropsychiatric symptoms and volumes of the brain regions typically affected by AD pathology.…”

Non‐neurological factors associated with serum neurofilament levels in the United States population

“…5 Concomitantly, changes in sNfL have been shown to correlate with disease progression in several other neurological diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, and traumatic brain injury. 6,7 There is also a growing body of studies of sNfL ª 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.…”

“…Concomitantly, changes in sNfL have been shown to correlate with disease progression in several other neurological diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, and traumatic brain injury. 6 , 7 There is also a growing body of studies of sNfL in non‐neurological settings. sNfL was increased in COVID‐19 patients on mechanical ventilation, and associated with unfavorable outcomes.…”