Plasma neurofilament light levels correlate with white matter damage prior to Alzheimer’s disease: results from ADNI

Nabizadeh, Fardin; Balabandian, Mohammad; Rostami, Mohammad Reza; Kankam, Samuel Berchi; Ranjbaran, Fatemeh; Pourhamzeh, Mahsa

doi:10.1007/s40520-022-02095-y

Cited by 11 publications

(9 citation statements)

References 49 publications

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“…In addition, a study focused on amyloid-positive cognitively impaired individuals (clinically de ned as having aMCI or AD dementia) found that higher concentrations of plasma and cerebrospinal uid NfL were associated with hypometabolism in AD-vulnerable regions at baseline and longitudinally (39). Regarding brain structural connectivity, Nabizadeh F demonstrated a signi cant association between plasma NfL levels and disrupted WM microstructure across the brain in distinct areas (14), which overlapped with the present study's ndings. Speci cally, higher plasma NfL was related to lower FA and higher RD, AD, and MD in the fornix, uncinate fasciculus, and hippocampal cingulum.…”

Section: Discussionsupporting

confidence: 85%

“…Previous studies have shown that NfL level and its rate of change in plasma are elevated in both sporadic and familial AD and are closely correlated with clinical symptoms and progression (8,11). Increased NfL levels have also been linked with various imaging biomarkers, including brain atrophy (hippocampal volume, entorhinal cortical thickness, ventricular volume, and temporal cortical thickness), decreased brain metabolism, and cross-sectional Aβ deposition (7,12,13,14).…”

Section: The Promise Of Neuro Lament Light Chain As a Biomarker For Admentioning

confidence: 99%

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Elevated plasma neurofilament light was associated with multi-modal neuroimaging features in Alzheimer’s Disease signature regions and predicted future tau deposition

Hu,

Shi,

et al. 2024

Preprint

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Background: Neurofilament Light (NfL) is a biomarker for early neurodegeneration in Alzheimer's disease (AD). This study aims to examine the association between plasma NfL and multi-modal neuroimaging features across the AD spectrum and whether NfL predicts future tau deposition. Methods: The present study recruited 517 participants comprising Aβ negative cognitively normal (CN-) participants (n = 135), CN + participants (n = 64), individuals with mild cognitive impairment (MCI) (n = 212), and those diagnosed with AD dementia (n = 106). All the participants underwent multi-modal neuroimaging examinations. Cross-sectional and longitudinal associations between plasma NfL and multi-modal neuro-imaging features were evaluated using partial correlation analysis and linear mixed effects models. We also used linear regression analysis to investigate the association of baseline plasma NfL with future PET tau load. Mediation analysis was used to explore whether the effect of NfL on cognition was mediated by these MRI markers. Results: The results showed that baseline NfL levels and the rate of change were associated with Aβ deposition, brain atrophy, brain connectome, glucose metabolism, and brain perfusion in AD signature regions. In both Aβ positive CN and MCI participants, baseline NfL showed a significant predictive value of elevating tau burden in the left medial orbitofrontal cortex and para-hippocampus. Lastly, the multi-modal neuroimaging features mediated the association between plasma NfL and cognitive performance. Conclusions: The study supports the association between plasma NfL and multi-modal neuroimaging features in AD-vulnerable regions and its predictive value for future tau deposition.

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Section: Discussionsupporting

confidence: 85%

Section: The Promise Of Neuro Lament Light Chain As a Biomarker For Admentioning

confidence: 99%

Elevated plasma neurofilament light was associated with multi-modal neuroimaging features in Alzheimer’s Disease signature regions and predicted future tau deposition

Hu,

Shi,

et al. 2024

Preprint

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“…The mechanisms underlying the impact of pathological molecules on cognitive decline along the AD continuum are complex. Building upon the possible mediating effect of neuroimaging biomarkers on the link between cognitive function and plasma biomarkers, several plasma biomarkers, such as pTau181 and NfL, have been found to potentially impact brain network efficiency by altering WM microstructure (Nabizadeh, Balabandian, et al, 2022; Nabizadeh, Pourhamzeh, et al, 2022). In our study, we delved deeper into the intricate connections between these biomarkers, particularly GFAP and NfL.…”

Section: Discussionmentioning

confidence: 99%

Relationship between topological efficiency of white matter structural connectome and plasma biomarkers across the Alzheimer's disease continuum

Zhang,

Chen,

Huang

et al. 2024

Human Brain Mapping

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Both plasma biomarkers and brain network topology have shown great potential in the early diagnosis of Alzheimer's disease (AD). However, the specific associations between plasma AD biomarkers, structural network topology, and cognition across the AD continuum have yet to be fully elucidated. This retrospective study evaluated participants from the Sino Longitudinal Study of Cognitive Decline cohort between September 2009 and October 2022 with available blood samples or 3.0‐T MRI brain scans. Plasma biomarker levels were measured using the Single Molecule Array platform, including β‐amyloid (Aβ), phosphorylated tau181 (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). The topological structure of brain white matter was assessed using network efficiency. Trend analyses were carried out to evaluate the alterations of the plasma markers and network efficiency with AD progression. Correlation and mediation analyses were conducted to further explore the relationships among plasma markers, network efficiency, and cognitive performance across the AD continuum. Among the plasma markers, GFAP emerged as the most sensitive marker (linear trend: t = 11.164, p = 3.59 × 10−24; quadratic trend: t = 7.708, p = 2.25 × 10−13; adjusted R2 = 0.475), followed by NfL (linear trend: t = 6.542, p = 2.9 × 10−10; quadratic trend: t = 3.896, p = 1.22 × 10−4; adjusted R2 = 0.330), p‐tau181 (linear trend: t = 8.452, p = 1.61 × 10−15; quadratic trend: t = 6.316, p = 1.05 × 10−9; adjusted R2 = 0.346) and Aβ42/Aβ40 (linear trend: t = −3.257, p = 1.27 × 10−3; quadratic trend: t = −1.662, p = 9.76 × 10−2; adjusted R2 = 0.101). Local efficiency decreased in brain regions across the frontal and temporal cortex and striatum. The principal component of local efficiency within these regions was correlated with GFAP (Pearson's R = −0.61, p = 6.3 × 10−7), NfL (R = −0.57, p = 6.4 × 10−6), and p‐tau181 (R = −0.48, p = 2.0 × 10−4). Moreover, network efficiency mediated the relationship between general cognition and GFAP (ab = −0.224, 95% confidence interval [CI] = [−0.417 to −0.029], p = .0196 for MMSE; ab = −0.198, 95% CI = [−0.42 to −0.003], p = .0438 for MOCA) or NfL (ab = −0.224, 95% CI = [−0.417 to −0.029], p = .0196 for MMSE; ab = −0.198, 95% CI = [−0.42 to −0.003], p = .0438 for MOCA). Our findings suggest that network efficiency mediates the association between plasma biomarkers, specifically GFAP and NfL, and cognitive performance in the context of AD progression, thus highlighting the potential utility of network‐plasma approaches for early detection, monitoring, and intervention strategies in the management of AD.

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“…Previous research indicates that NfL is a non-specific marker of neurodegeneration, with increased levels in CSF observed in various dementias [24]. Studies show that elevated levels of NfL in CSF and plasma are linked to AD-related neuroimaging findings, including hippocampal atrophy, ventricular enlargement, and cortical thinning [25][26][27]. Serum NfL levels also increase in healthy aging people and predict brain volume loss [28].…”

Section: Discussionmentioning

confidence: 99%

Axonal degeneration serum markers and temporal lobe atrophy in Alzheimer’s dementia continuum: a longitudinal study of plasma neurofilament light and tensor-based morphometry

Khodadadi,

Amirkhani,

Nouri

et al. 2024

Preprint

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The plasma neurofilament light chain (NfL), an axonal cytoskeleton protein, increases in Alzheimer disease and was therefore proposed as a blood-based biomarker of the disease. Tensor-based morphometry (TBM) is an MR based modality that identifies local volume changes in the brain. Herein, we aimed to investigate whether plasma NfL measures can predict TBM findings derived from temporal lobe of brain in a one-year follow-up and which biomarker can predict cognitive function. A total of 480 participants with Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal cognition (CN) were found eligible for inclusion from The Alzheimer's Disease Neuroimaging Initiative (ADNI) database. There was a significant negative association between plasma NfL and TBM only when all subjects were pooled together at baseline (β = -0.139, P= 0.004). After one-year follow-up, 30 subjects with MCI converted to AD (MCI-AD) and others remained unchanged (CN, MCI, AD). Plasma NfL levels elevated significantly only in MCI group after one year (P<0.001). We found a significant reduction in TBM measurements at first-year compared to baseline in all groups (P<0.001 for all groups). Additionally, TBM average change rate was significantly higher in MCI-AD and AD groups (P<0.001 for both); however, plasma NfL average change rate was not significantly different between groups. TBM was significantly correlated with MMSE, MoCA, ADAS-11 and ADAS-13 scores in both MCI and AD patients at baseline and after one year, whereas plasma NfL was not. Overall, our findings indicate that plasma NfL is not reliably associated with TBM, and is less effective and sensitive than TBM in predicting dementia progression and cognitive performance. Hence, TBM reduction is not reflected in plasma NfL increment after one year follow-up.

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Plasma neurofilament light levels correlate with white matter damage prior to Alzheimer’s disease: results from ADNI

Cited by 11 publications

References 49 publications

Elevated plasma neurofilament light was associated with multi-modal neuroimaging features in Alzheimer’s Disease signature regions and predicted future tau deposition

Elevated plasma neurofilament light was associated with multi-modal neuroimaging features in Alzheimer’s Disease signature regions and predicted future tau deposition

Relationship between topological efficiency of white matter structural connectome and plasma biomarkers across the Alzheimer's disease continuum

Axonal degeneration serum markers and temporal lobe atrophy in Alzheimer’s dementia continuum: a longitudinal study of plasma neurofilament light and tensor-based morphometry

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