The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed
arteriolosclerosis) is common in the brains of older people and is associated with
lacunar infarcts,
leukoaraiosis, and
vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the
plasma proteins fibrinogen and
immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal
Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of
fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with
fibrinogen and
immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of
fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001).
Fibrinogen in DGM showed a modest association with a history of
hypertension; DWM
fibrinogen was associated with
dementia and
cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with
leukoaraiosis identified in life (p < 0.05), but
fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.