Vasculocentric Axonal NfH in Small Vessel Disease

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Cerebral small vessel disease (SVD) contributes to lacunar stroke and vascular cognitive impairment in older adults.
• The precise mechanisms linking SVD vessel pathology to brain damage remain unclear.
• Neurofilaments, particularly neurofilament-light (NfL), are recognized biomarkers in neurological conditions.

Purpose of the Study:

• To investigate the role of hyperphosphorylated neurofilament-heavy (pNfH) in the subcortical white matter of aging brains.
• To characterize the pattern of pNfH deposition, specifically focusing on vasculocentric localization.
• To compare the prevalence of vasculocentric pNfH in individuals with SVD versus severe Alzheimer disease (AD).

Main Methods:

• Immunohistochemical analysis of subcortical frontal and parietal white matter tissue.
• Quantification of pNfH immunolabeling and its concentration around penetrating arteries.
• Comparison of pNfH patterns in young controls, aged controls, and patients with SVD or severe AD (n=52).

Main Results:

• Axonal pNfH deposition was infrequent in young adults but prevalent in older individuals across all groups (controls, SVD, AD).
• A distinct pattern of pNfH accumulation, concentrated around small penetrating arteries (vasculocentric), was observed.
• This vasculocentric pNfH pattern was significantly more common in older adults with SVD compared to those with severe AD (p=0.004).

Conclusions:

• Axonal pNfH represents a characteristic finding in the subcortical white matter of aged brains.
• Vasculocentric axonal pNfH is identified as a novel parenchymal lesion.
• The co-localization with SVD arteriopathy suggests that vasculocentric pNfH may arise as a consequence of SVD-related vessel pathology.