scholarly journals Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lingxiao He ◽  
John E. Morley ◽  
Geetika Aggarwal ◽  
Andrew D. Nguyen ◽  
Bruno Vellas ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Light Chain ◽  
Cognitive Functions ◽  
Linear Models ◽  
Cognitive Status ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
State Examination

AbstractNeurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer’s Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β =  − 0.007, 95% CI [− 0.013, − 0.001]; CCS: β =  − 0.003, 95% CI [− 0.006, − 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β =  − 0.003, 95% CI [− 0.005, − 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β =  − 0.07, 95% CI [− 0.12, − 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI.

scholarly journals Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jordan D. Marks ◽  
Jeremy A. Syrjanen ◽  
Jonathan Graff-Radford ◽  
Ronald C. Petersen ◽  
Mary M. Machulda ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Temporal Cortex ◽  
Cognitive Status ◽  
White Matter Hyperintensity ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Total Tau ◽  
T Tau

Abstract Background Total tau protein (T-Tau) and neurofilament light chain (NfL) have emerged as candidate plasma biomarkers of neurodegeneration, but studies have not compared how these biomarkers cross-sectionally or longitudinally associate with cognitive and neuroimaging measures. We therefore compared plasma T-Tau and NfL as cross-sectional and longitudinal markers of (1) global and domain-specific cognitive decline and (2) neuroimaging markers of cortical thickness, hippocampal volume, white matter integrity, and white matter hyperintensity volume. Methods We included 995 participants without dementia who were enrolled in the Mayo Clinic Study of Aging cohort. All had concurrent plasma NfL and T-tau, cognitive status, and neuroimaging data. Follow-up was repeated approximately every 15 months for a median of 6.2 years. Plasma NfL and T-tau were measured on the Simoa-HD1 Platform. Linear mixed effects models adjusted for age, sex, and education examined associations between baseline z-scored plasma NfL or T-tau and cognitive or neuroimaging outcomes. Analyses were replicated in Alzheimer’s Disease Neuroimaging Initiative (ADNI) among 387 participants without dementia followed for a median of 3.0 years. Results At baseline, plasma NfL was more strongly associated with all cognitive and neuroimaging outcomes. The combination of having both elevated NfL and T-tau at baseline, compared to elevated levels of either alone, was more strongly associated at cross-section with worse global cognition and memory, and with neuroimaging measures including temporal cortex thickness and increased number of infarcts. In longitudinal analyses, baseline plasma T-tau did not add to the prognostic value of baseline plasma NfL. Results using ADNI data were similar. Conclusions Our results indicate plasma NfL had better utility as a prognostic marker of cognitive decline and neuroimaging changes. Plasma T-tau added cross-sectional value to NfL in specific contexts. Trial registration Not applicable

Associations of plasma neurofilament light chain and progranulin with frailty in older adults

2021 ◽  
Author(s):  
Wan‐Hsuan Lu ◽  
Kelly Virecoulon Giudici ◽  
Sophie Guyonnet ◽  
Geetika Aggarwal ◽  
Andrew D. Nguyen ◽  
...  
Keyword(s):  
Older Adults ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Neurofilament light chain in the vitreous humor of the eye

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Manju L. Subramanian ◽  
Viha Vig ◽  
Jaeyoon Chung ◽  
Marissa G. Fiorello ◽  
Weiming Xia ◽  
...  
Keyword(s):  
Sex Education ◽  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Light Chain ◽  
Systemic Disease ◽  
Vitreous Humor ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
T Tau

Abstract Background Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. Methods This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5–1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (Aβ), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins, APOE genotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. Results NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of Aβ40 (p = 7.7 × 10−5), Aβ42 (p = 2.8 × 10−4), and t-tau (p = 5.5 × 10−7), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15, p = 5.3 × 10−4), IL-16 (p = 2.2 × 10−4), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10−4), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10−6), Vegf-C (p = 8.6 × 10−6), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10−4), Tie-2 (p = 6.3 × 10−4), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10−4). Conclusion NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients’ clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.

P3-251: SERUM NEUROFILAMENT LIGHT CHAIN LEVELS ARE ASSOCIATED WITH CSF NEUROFILAMENT LIGHT CHAIN, COGNITIVE STATUS, AND DISEASE PROGRESSION IN AUTOSOMAL DOMINANT AD

2006 ◽  
Vol 14 (7S_Part_22) ◽  
pp. P1170-P1170 ◽  
Author(s):  
Oliver Preische ◽  
Stephanie A. Schultz ◽  
Anja Apel ◽  
Jens Kuhle ◽  
Brian A. Gordon ◽  
...  
Keyword(s):  
Disease Progression ◽  
Light Chain ◽  
Autosomal Dominant ◽  
Cognitive Status ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Renal function is associated with blood neurofilament light chain level in older adults

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shoshin Akamine ◽  
Noriko Marutani ◽  
Daisuke Kanayama ◽  
Shiho Gotoh ◽  
Riki Maruyama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Older Adults ◽  
Renal Function ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Precise Evaluation ◽  
Patients With Diabetes ◽  
Healthy Participants ◽  
Chain Level

AbstractNeurofilament light chain (NfL) is a novel biomarker of neurodegenerative diseases. It is detectable in the peripheral blood, allowing low-invasive assessment of early signs of neurodegeneration. The level of NfL gradually increases with age; however, what other factors affect it remains unclear. The present study examined the association between blood NfL level and renal function among healthy participants undergoing a health check (n = 43, serum NfL) and patients with diabetes mellitus (n = 188, plasma NfL). All participants were 60 years of age or older; none were diagnosed with dementia. In each group, levels of blood NfL and serum creatinine significantly correlated (coefficient r = 0.50, 0.56). These associations remained statistically significant even after adjustment for age, sex, and body mass index. These findings indicate that blood NfL level might be partially affected by renal function. We recommend measuring renal function for a more precise evaluation of neuroaxonal damage, in particular, among older adults.

scholarly journals Elevated Levels of Serum Neurofilament Light Chain Associated with Cognitive Impairment in Vascular Dementia

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Weibin Ma ◽  
Jingjing Zhang ◽  
Jialei Xu ◽  
Depeng Feng ◽  
Xiaoling Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Single Molecule ◽  
Light Chain ◽  
Peripheral Blood ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Biochemical Characteristics ◽  
Significant Difference

Objective. Vascular dementia (VaD) is a progressive neurodegenerative disease with cognitive decline caused by cerebrovascular factors. Despite the great progress made in the past decade, VaD still lacks effective treatments and peripheral blood biomarkers. In this study, we tested the level of peripheral blood neurofilament light chain (NfL) in VaD patients and explored its relationship with cognitive impairment. Method. A total of 176 study subjects including 80 normal controls (NC) and 96 VaD patients were included in our study. Upon admission, we collected clinical and biochemical characteristics of all research subjects. We also evaluate the Montreal cognitive assessment scale (MoCA) scores of all subjects. The serum NfL level was measured by the single-molecule array (Simoa) method. Results. The years of education in the NC group and VaD group were ( 11.65 ± 3.04 ) years and ( 10.53 ± 3.87 ) years, respectively. Compared with VaD patients, the NC group has a higher level of education ( p = 0.037 ). Furthermore, the results of Simoa indicated that VaD subjects had higher serum NfL levels compared with the NC group [( 8.49 ± 2.37 ) pg/ml vs. ( 19.26 ± 4.71 ) pg/ml, p < 0.001 ]. In terms of other clinical and biochemical characteristics, there was no significant difference between VaD and NC. The Spearman correlation analysis indicated that educational years have a significant positive correlation with MoCA scores ( r = 0.238 , p = 0.041 ), while age and serum NfL levels have a significantly negative correlation with MoCA scores (age: r = − 0.213 , p = 0.040 ; NfL: r = − 0.395 , p = 0.027 ). However, further multiple regression analysis showed that only serum NfL level might serve as an independent risk factor for cognitive decline in VaD ( β = 0.317 , p = 0.021 ). Conclusion. The serum NfL levels in VaD subjects are significantly elevated, which may be used as a potential peripheral blood marker for predicting cognitive impairment in patients with VaD.

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