Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of cognitively impaired patients with concomitant cerebral small vessel disease

Author:

Chong Joyce R.12,Hilal Saima123,Ashton Nicholas J.4567,Karikari Thomas K.48,Reilhac Anthonin9,Vrooman Henri10,Schöll Michael4511,Zetterberg Henrik411121314,Blennow Kaj413,Chen Christopher P.1215,Lai Mitchell K. P.12

Affiliation:

1. Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Kent Ridge Singapore

2. Memory, Aging and Cognition Centre National University Health Systems Kent Ridge Singapore

3. Saw Swee Hock School of Public Health National University of Singapore and National University Health System Kent Ridge Singapore

4. Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden

5. Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden

6. King's College London Institute of Psychiatry Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute London UK

7. NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation London UK

8. Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA

9. Clinical Imaging Research Centre Yong Loo Lin School of Medicine National University of Singapore Kent Ridge Singapore

10. Department of Radiology and Nuclear Medicine Erasmus Medical Center Rotterdam the Netherlands

11. Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology London UK

12. UK Dementia Research Institute at UCL London UK

13. Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Gothenburg Sweden

14. Hong Kong Center for Neurodegenerative Diseases the Hong Kong University of Science and Technology Hong Kong Science Park Shatin New Territories Hong Kong SAR China

15. Department of Psychological Medicine Yong Loo Lin School of Medicine National University of Singapore Kent Ridge Singapore

Abstract

AbstractIntroductionPlasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non‐dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (Aβ) burden on plasma NfL are lacking.MethodsAssociations were tested between plasma NfL and brain Aβ, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds.ResultsWe found that participants with either MTA (defined as MTA score ≥2; neurodegeneration [N]+WMH−) or WMH (cut‐off for log‐transformed WMH volume at 50th percentile; N−WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH−, N−WMH+, and N−WMH− individuals.DiscussionPlasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment.

Funder

National Medical Research Council

Publisher

Wiley

Subject

Psychiatry and Mental health,Neurology (clinical)

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