Real-world applicability of glial fibrillary acidic protein and neurofilament light chain in Alzheimer’s disease

Abstract

Background: Blood-based biomarkers may add a great benefit in detecting the earliest neuropathological changes in patients with Alzheimer’s disease (AD). We examined the utility of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) regarding clinical diagnosis and differentiation between amyloid positive and negative patients. To evaluate the practical application of these biomarkers in a routine clinical setting, we conducted this study in a heterogeneous memory-clinic population.Methods: We included 167 patients in this retrospective cross-sectional study, 123 patients with an objective cognitive decline [mild cognitive impairment (MCI) due to AD, n = 63, and AD-dementia, n = 60] and 44 age-matched healthy controls (HC). Cerebrospinal fluid (CSF) and plasma concentrations of NfL and GFAP were measured with single molecule array (SIMOA®) technology using the Neurology 2-Plex B kit from Quanterix. To assess the discriminatory potential of different biomarkers, age- and sex-adjusted receiver operating characteristic (ROC) curves were calculated and the area under the curve (AUC) of each model was compared.Results: We constructed a panel combining plasma NfL and GFAP with known AD risk factors (Combination panel: age+sex+APOE4+GFAP+NfL). With an AUC of 91.6% (95%CI = 0.85–0.98) for HC vs. AD and 81.7% (95%CI = 0.73–0.90) for HC vs. MCI as well as an AUC of 87.5% (95%CI = 0.73–0.96) in terms of predicting amyloid positivity, this panel showed a promising discriminatory power to differentiate these populations.Conclusion: The combination of plasma GFAP and NfL with well-established risk factors discerns amyloid positive from negative patients and could potentially be applied to identify patients who would benefit from a more invasive assessment of amyloid pathology. In the future, improved prediction of amyloid positivity with a noninvasive test may decrease the number and costs of a more invasive or expensive diagnostic approach.

Relationship between increased serum neurofilament light chain and glial fibrillary acidic protein levels with non‐motor symptoms in patients with Parkinson's disease

“…This may be attributable to the fact that the gastrointestinal tract promotes neuroinflammation and neurodegeneration by altering the microbiome‐brain‐gut axis. Notably, in addition to PD, the potential association between NFL and cognitive impairment has also been reported for a variety of neurodegenerative diseases such as Alzheimer's disease, 31 frontotemporal dementia, 32 and dementia with Lewy bodies, 33 which indicates that mechanisms by which NFL influences non‐motor progression are not disease‐specific. In summary, NFL is a sensitive but non‐disease‐specific biomarker that is increased in various neurological disorders associated with axonal injury, and its potential diagnostic value should be supplemented by further neurological tests, disease‐specific biomarkers, and brain imaging results.…”

Cross‐sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease

“…While GFAP differentiated NC and MCI from those with AD dementia, it did not differentiate NC from MCI. Parvizi et al 12 . assessed the diagnostic discrimination of plasma GFAP and likewise did not observe significant findings when separating cognitively impaired individuals into MCI and AD dementia.…”

“…While GFAP differentiated NC and MCI from those with AD dementia, it did not differentiate NC from MCI. Parvizi et al 12 assessed the diagnostic discrimination of plasma GFAP and likewise did not observe significant findings when separating cognitively impaired individuals into MCI and AD dementia. There is growing evidence supporting plasma GFAP as one of the first pre-clinical markers, 6,14,19 observable 8 to 16 years before dementia onset.…”

“…Blood-based GFAP has accurately discriminated individuals with normal cognition (NC) from AD dementia and is correlated with CSF measurements of Aβ. [10][11][12][13][14][15] Plasma GFAP detected AD dementia more accurately than CSF GFAP suggesting that brain release of GFAP into the bloodstream is an early event in AD and posits an opportunity for timelier in vivo detection. 13,16,17 Longitudinal studies support plasma GFAP to monitor the progression of AD dementia.…”

Plasma Biomarkers of Alzheimer’s Disease: A Review of Available Assays, Recent Developments, and Implications for Clinical Practice

“…Improvements have been made in developing more sensitive and specific assays that measure ␤-synuclein levels in blood [100]. This synaptic biomarker has its levels increased as an early sign of synaptic degeneration in AD [101,102]. It has also been linked to plasma levels of p-tau181 and A␤, suggesting an association with amyloid pathology.…”