Histopathological Correlates of Lobar Microbleeds in False‐Positive Cerebral Amyloid Angiopathy Cases

Abstract

ObjectiveA definite diagnosis of cerebral amyloid angiopathy (CAA), characterized by the accumulation of Amyloid‐β in walls of cerebral small vessels, can only be obtained through pathological examination. A diagnosis of probable CAA during life relies on the presence of haemorrhagic markers, including lobar cerebral microbleeds (CMBs). The aim of this project was to study the histopathological correlates of lobar CMBs in false‐positive CAA cases.MethodsIn three patients who met criteria for probable CAA during life, but showed no CAA upon neuropathological examination, lobar CMBs were counted on ex vivo 3 T MRI and on ex vivo 7 T MRI. Areas with lobar CMBs were next sampled and cut in serial sections, on which the CMBs were then identified.ResultsCollectively, there were 25 lobar CMBs on in vivo MRI and 22 on ex vivo 3 T MRI of the analysed hemispheres. On ex vivo MRI we targeted 12 CMBs for sampling and definite histopathological correlates were retrieved for 9 of them of which seven were true CMBs. No CAA was found on any of the serial sections. The ‘culprit vessels’ associated with the true CMBs instead showed moderate to severe arteriolosclerosis. Furthermore, CMBs in false‐positive CAA cases tended to be located more often in the juxtacortical or subcortical white matter, than in the cortical ribbon.InterpretationThese findings suggest that arteriolosclerosis can generate lobar CMBs and that more detailed investigations into the exact localization of CMBs with respect to the cortical ribbon could potentially aid the diagnosis of CAA during life.This article is protected by copyright. All rights reserved.

Association of Long-Term Blood Pressure Variability with Cerebral Amyloid Angiopathy-related Brain Injury and Cognitive Decline

“…Additionally, alternative mechanistic explanations may exist, particularly due to improving understanding that both CAA and hypertensive SVD (arteriosclerosis) may interact at the pathophysiological level to cause brain injury. 45 These two common types of SVD often co-occur, and further studies are needed to disentangle the SVD-type specific effects on brain tissue.…”

Associations of Cerebral Small Vessel Disease and Chronic Kidney Disease in Patients With Acute Intracerebral Hemorrhage

“…4 A "mixed SVD" pattern may be caused either by coexistence of arteriolosclerosis and CAA or by severe arteriolosclerosis alone 5 ; a recent histopathologic study provides evidence that at least some lobar microbleeds are caused by arteriolosclerosis. 6 Both CAA and arteriolosclerosis are strongly associated with age, and arteriolosclerosis is strongly associated with vascular risk factors, particularly hypertension. Chronic kidney disease (CKD) is an independent risk factor of ICH 7 and is associated with SVD, particularly in community-based populations, such as those with hypertension or diabetes.…”

18F Flutemetamol-PET Aided Classification of Cerebral Amyloid Angiopathy

“…Neuroimaging still lacks specificity to distinguish CAA from arteriolosclerosis, and deep (d)CMB prevents the diagnosis of CAA as per criteria. 2 PET imaging with amyloid tracers may represent a noninvasive method to enhance diagnostic accuracy 6,7 and identify the underlying etiology 8 in suspected CAA cases.…”

“…PET imaging with amyloid tracers may represent a noninvasive method to enhance diagnostic accuracy 6,7 and identify the underlying etiology 8 in suspected CAA cases.…”