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

Article type: Research Article

Authors: Chatterjee, Pratishtha^{a; b; c; 1} | Goozee, Kathryn^{a; b; c; d; e; g; 1} | Sohrabi, Hamid R.^{a; b; e; f} | Shen, Kaikai^h | Shah, Tejal^{a; b; f} | Asih, Prita R.^{c; i} | Dave, Preeti^{a; d} | ManYan, Candice^d | Taddei, Kevin^{b; f} | Chung, Roger^a | Zetterberg, Henrik^{j; k; l; m} | Blennow, Kaj^{j; k} | Martins, Ralph N.^{a; b; c; e; f; g; *}

Affiliations: [a] Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia | [b] School of Medical Health and Sciences, Edith Cowan University, Joondalup, WA, Australia | [c] KaRa Institute of Neurological Disease, Sydney, Macquarie Park, Australia | [d] Department of Clinical Research, Anglicare, Sydney, Castle Hill, NSW, Australia | [e] School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia | [f] Australian Alzheimer Research Foundation, Nedlands, WA, Australia | [g] The Cooperative Research Centre for Mental Health, Carlton South, Australia | [h] Australian eHealth Research Centre, CSIRO, Floreat, Australia | [i] School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia | [j] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden | [k] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [l] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK | [m] UK Dementia Research Institute at UCL, London, UK

Correspondence: [*] Correspondence to: Ralph N. Martins, PhD, School of Medical Science, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia. Tel.: +61 8 6304 5456; Fax: +61 8 6304 5851; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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.

Keywords: Alzheimer’s disease, blood, neurofilaments, positron emission tomography, cognitive function, episodic memory, executive function, verbal memory, visual memory

DOI: 10.3233/JAD-180025

Journal: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 479-487, 2018