Cerebral microbleeds: Spatial distribution implications

Abstract

Cerebral microbleeds are considered an imaging marker of cerebral small vessel disease. The location of microbleeds is thought to reflect the underlying pathology. Microbleeds in the deep and infratentorial region are thought to reflect hypertensive arteriopathy whereas lobar microbleeds are associated clinically with cerebral amyloid angiopathy (CAA). Aside from patient populations, microbleeds are frequently observed in seemingly asymptomatic populations. Moreover, many elderly, both in clinical and preclinical populations, have multiple coexisting pathologies in their brains, which complicates the interpretation of cerebral microbleeds, especially early in the clinical course. In this commentary, we discuss the influence of the strongest genetic risk factor for CAA, Apolipoprotein E (APOE), in the spatial distribution of microbleeds, and we additionally address issues in interpretation and implication of the location of microbleeds in clinical and asymptomatic populations.

Monoaminergic neuropathology in Alzheimer’s disease

“…The upregulation of N-terminal fragment of APP would, under such a scheme, be part of the attempt to prevent clotting in the hemorrhaged region caused by blood contact with the brain tissue (if the coagulation cascade would exist in the brain, vascular blockage would lead to ischemic stroke and permanent neuronal death because the brain, unlike other tissues, has close to zero ability to replace terminally differentiated neurons), whereas Aβ would be a vascular sealant, anticoagulant and remodeling molecule (Atwood et al, 2003). This would also explain close and intimate relationships between plaques and blood vessels in transgenic mouse models (Kumar-Singh et al, 2005), the presence of iron in every plaque (Falangola et al, 2005), and the association of APOE ε2 genotype with cerebral hemorrhage (McCarron and Nicoll, 2000; Loehrer et al, 2014; Charidimou et al, 2015). Unlike microbleeds in the deep and infratentorial regions, which are thought to reflect hypertensive arteriopathy, lobar microbleeds are associated clinically with CAA, and frequently observed in seemingly asymptomatic populations (Loehrer et al, 2014).…”

“…This would also explain close and intimate relationships between plaques and blood vessels in transgenic mouse models (Kumar-Singh et al, 2005), the presence of iron in every plaque (Falangola et al, 2005), and the association of APOE ε2 genotype with cerebral hemorrhage (McCarron and Nicoll, 2000; Loehrer et al, 2014; Charidimou et al, 2015). Unlike microbleeds in the deep and infratentorial regions, which are thought to reflect hypertensive arteriopathy, lobar microbleeds are associated clinically with CAA, and frequently observed in seemingly asymptomatic populations (Loehrer et al, 2014). If the above concept is true, it would also be useful to explain the fact why about around 40% of AD patients have normotensive hydrocephalus (because CAA would prevent the proper exchange of water and ions through the blood-brain barrier, BBB), and why about 40% of adult patients with idiopathic chronic normal pressure hydrocephalus have histological lesions characteristic of AD, as revealed from cortical biopsies (Golomb et al, 2000).…”