Vasculocentric Axonal NfH in Small Vessel Disease

Author:

Anad Adam1,Barker Miriam K2,Katanga Jessica A1,Arfanakis Konstantinos23,Bridges Leslie R14,Esiri Margaret M5,Isaacs Jeremy D16,Prpar Mihevc Sonja7,Pereira Anthony C16,Schneider Julie A1,Hainsworth Atticus H16ORCID

Affiliation:

1. From the Molecular and Clinical Sciences Research Institute, St George’s University of London, London, UK (AA, MKB, JAK, LRB, JDI, ACP, AHH)

2. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA (KA, JAS)

3. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA (KA)

4. Department of Cellular Pathology, St George’s University Hospitals NHS Foundation Trust, London, UK (LRB)

5. Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK (MME)

6. Department of Neurology, St George’s University Hospitals NHS Foundation Trust, London, UK (JDI, ACP, AHH)

7. Institute for Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia (SPM)

Abstract

Abstract Cerebral small vessel disease (SVD) causes lacunar stroke and vascular cognitive impairment in older people. The pathogenic pathways from vessel pathology to parenchymal damage in SVD are unknown. Neurofilaments are axonal structural proteins. Neurofilament-light (NfL) is an emerging biomarker for neurological disease. Here, we examined the high molecular weight form neurofilament-heavy (NfH) and quantified a characteristic pattern of peri-arterial (vasculocentric) NfH labeling. Subcortical frontal and parietal white matter from young adult controls, aged controls, and older people with SVD or severe Alzheimer disease (n = 52) was immunohistochemically labeled for hyperphosphorylated NfH (pNfH). The extent of pNfH immunolabeling and the degree of vasculocentric axonal pNfH were quantified. Axonal pNfH immunolabeling was sparse in young adults but a common finding in older persons (controls, SVD, or AD). Axonal pNfH was often markedly concentrated around small penetrating arteries. This vasculocentric feature was more common in older people with SVD than in those with severe AD (p = 0.004). We conclude that axonal pNfH is a feature of subcortical white matter in aged brains. Vasculocentric axonal pNfH is a novel parenchymal lesion that is co-located with SVD arteriopathy and could be a consequence of vessel pathology.

Funder

Alzheimer’s Society

Alzheimer’s Drug Discovery Foundation

Alzheimer’s Research UK

UK Medical Research Council

National Institute of Neurological Disorders and Stroke

European Regional Development Fund

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Neurology (clinical),Neurology,General Medicine,Pathology and Forensic Medicine

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