Pratishtha Chatterjee1,2,3, Kathryn Goozee1,2,3,4,5,6, Hamid R Sohrabi1,2,5,7, Kaikai Shen8, Tejal Shah1,2,7, Prita R Asih3,9, Preeti Dave1,4, Candice ManYan4, Kevin Taddei2,7, Roger Chung1, Henrik Zetterberg10,11,12,13, Kaj Blennow10,11, Ralph N Martins1,2,3,5,7,6. 1. Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia. 2. School of Medical Health and Sciences, Edith Cowan University, Joondalup, WA, Australia. 3. KaRa Institute of Neurological Disease, Sydney, Macquarie Park, Australia. 4. Department of Clinical Research, Anglicare, Sydney, Castle Hill, NSW, Australia. 5. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia. 6. The Cooperative Research Centre for Mental Health, Carlton South, Australia. 7. Australian Alzheimer Research Foundation, Nedlands, WA, Australia. 8. Australian eHealth Research Centre, CSIRO, Floreat, Australia. 9. School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia. 10. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden. 11. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 12. Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK. 13. UK Dementia Research Institute at UCL, London, UK.
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 APOEɛ4 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.
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 APOEɛ4 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.
Authors: Rohith N Thota; Pratishtha Chatterjee; Steve Pedrini; Eugene Hone; Jessica J A Ferguson; Manohar L Garg; Ralph N Martins Journal: Front Endocrinol (Lausanne) Date: 2022-06-20 Impact factor: 6.055
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Authors: Inge M W Verberk; Rosalinde E Slot; Sander C J Verfaillie; Hans Heijst; Niels D Prins; Bart N M van Berckel; Philip Scheltens; Charlotte E Teunissen; Wiesje M van der Flier Journal: Ann Neurol Date: 2018-10-04 Impact factor: 10.422
Authors: Pratishtha Chatterjee; Henrik Zetterberg; Kathryn Goozee; Chai K Lim; Kelly R Jacobs; Nicholas J Ashton; Abdul Hye; Steve Pedrini; Hamid R Sohrabi; Tejal Shah; Prita R Asih; Preeti Dave; Kaikai Shen; Kevin Taddei; David B Lovejoy; Gilles J Guillemin; Kaj Blennow; Ralph N Martins Journal: J Neuroinflammation Date: 2019-10-10 Impact factor: 8.322
Authors: Nicholas J Ashton; Antoine Leuzy; Yau Mun Lim; Claire Troakes; Tibor Hortobágyi; Kina Höglund; Dag Aarsland; Simon Lovestone; Michael Schöll; Kaj Blennow; Henrik Zetterberg; Abdul Hye Journal: Acta Neuropathol Commun Date: 2019-01-09 Impact factor: 7.801