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Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-beta Load and Cognitive Performance in Cognitively Normal Elderly Participants

Chatterjee, P; Goozee, K; Sohrabi, HR; Shen, K; Shah, T; Asih, PR; Dave, P; ... Martins, RN; + view all (2018) Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-beta Load and Cognitive Performance in Cognitively Normal Elderly Participants. Journal of Alzheimer's Disease , 63 (2) pp. 479-487. 10.3233/JAD-180025. Green open access

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Abstract

BACKGROUND: The disruption of neurofilament, an axonal cytoskeletal protein, in neurodegenerative conditions may result in neuronal damage and its release into the cerebrospinal fluid and blood. In Alzheimer’s disease (AD), neurofilament light chain (NFL), a neurofilament subunit, is elevated in the cerebrospinal fluid and blood. OBJECTIVE: Investigate the association of plasma NFL with preclinical-AD features, such as high neocortical amyloid-β load (NAL) and subjective memory complaints, and cognitive performance in cognitively normal older adults. METHODS: Plasma NFL concentrations were measured employing the single molecule array platform in participants from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort, aged 65– 90 years. Participants underwent a battery of neuropsychological testing to evaluate cognitive performance and were categorized as low NAL (NAL-, n = 65) and high NAL (NAL+, n = 35) assessed via PET, and further stratified into subjective memory complainers (SMC; nNAL- = 51, nNAL+ = 25) and non-SMC (nNAL- = 14, nNAL+ = 10) based on the Memory Assessment Clinic– Questionnaire. RESULTS: Plasma NFL inversely correlated with cognitive performance. No significant difference in NFL was observed between NAL+ and NAL- participants; however, within APOE ɛ4 non-carriers, higher NAL was observed in individuals with NFL concentrations within quartiles 3 and 4 (versus quartile 1). Additionally, within the NAL+ participants, SMC had a trend of higher NFL compared to non-SMC. CONCLUSION: Plasma NFL is inversely associated with cognitive performance in elderly individuals. While plasma NFL may not reflect NAL in individuals with normal global cognition, the current observations indicate that onset of axonal injury, reflected by increased plasma NFL, within the preclinical phase of AD may contribute to the pathogenesis of AD.

Type: Article
Title: Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-beta Load and Cognitive Performance in Cognitively Normal Elderly Participants
Open access status: An open access version is available from UCL Discovery
DOI: 10.3233/JAD-180025
Publisher version: http://dx.doi.org/10.3233/JAD-180025
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Alzheimer's disease, blood, neurofilaments, positron emission tomography, cognitive function, episodic memory, executive function, verbal memory, visual memory, PRECLINICAL ALZHEIMERS-DISEASE, CEREBROSPINAL-FLUID, FRONTOTEMPORAL DEMENTIA, DIFFERENTIAL-DIAGNOSIS, NEURODEGENERATION, DEGENERATION, BIOMARKERS, DISORDER
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10057518
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