Journal
NEUROLOGY
Volume 89, Issue 21, Pages 2167-2175Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000004667
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Funding
- MRC
- Brain Exit Fellowship
- Wolfson Foundation
- NIHR Queen Square Dementia Biomedical Research Unit (BRU)
- Torsten Soderberg Foundation at the Swedish Royal Academy of Sciences
- Research Council Sweden
- Brain Foundation Sweden
- Alzheimer Foundation Sweden
- NIHR Queen Square Dementia BRU
- MRC Dementias Platform UK
- Leonard Wolfson Experimental Neurology Centre
- Department of Health's NIHR Biomedical Research Centres funding scheme
- European Research Council
- Swedish Research Council
- Frimurarestiftelsen
- VINNOVA
- MRC [MR/M003108/1, MC_U123160651, G0900421, UKDRI-1003, MR/L023784/1, MR/L023784/2] Funding Source: UKRI
- Medical Research Council [MC_U123160651, MR/M003108/1, G0900421, MR/L023784/2, MR/L023784/1, UKDRI-1003] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10134, NF-SI-0512-10033] Funding Source: researchfish
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Objectives: To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. Methods: We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. Results: Nineteen of the asymptomatic participants were mutation carriers (mean EYO 29.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic (p < 0.0001) and presymptomatic mutation carriers (p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (r = 0.81, p < 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (r = -0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (r = 0.79, p < 0.0001), baseline brain volume (r = -0.62, p = 0.0002), and whole-brain atrophy rate (r = 0.53, p = 0.01). Conclusions: Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration.
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