No neuropathological evidence for a direct topographical relation between microbleeds and cerebral amyloid angiopathy.
BACKGROUND
Cerebral microbleeds correspond to blood breakdown products, including hemosiderin-containing macrophages around small vessels on histological examination. Superficial lobar cerebral microbleeds are increasingly recognized on MRI as a biomarker of cerebral amyloid angiopathy but the direct association between amyloid-laden vessels burden and cerebral microbleeds has yet to be validated neuropathologically. To address this issue, we examined the frequency of histopathologically-defined cerebral microbleeds in different brain regions and their relationship with cerebral amyloid angiopathy in a large autopsy population.


RESULTS
The frontal, parietal and occipital cortex as well as the adjacent white matter and basal ganglia of 113 consecutive autopsies were examined. Cerebral microbleedss were identified on haematoxylin-eosin-stained histological slides, cerebral amyloid angiopathy using anti-amyloid antibody. Cerebral microbleeds were present in 92.9 % of the cases and cerebral amyloid angiopathy in 44.3 % of them. Cerebral microbleeds were more frequent in parietal and frontal lobes followed by the occipital region and basal ganglia. In contrast, cerebral amyloid angiopathy was most frequent in the occipital lobe. There was no significant topographical association between cerebral amyloid angiopathy presence or severity and cerebral microbleeds in any brain region. In lobar areas, cerebral amyloid angiopathy was found in the cortex, predominantly affecting pial arteries and their superficial cortical branches, in contrast to microbleeds which were mainly in the white matter and occurred around deeper arteries and arterioles, including the subcortical segment of long penetrating branches of pial vessels.


CONCLUSIONS
Our study does not support a direct relation between cerebral microbleeds and cerebral amyloid angiopathy burden at the neuropathological level, raising intriguing questions on the potential pathophysiological mechanisms of cerebral microbleeds in the context of cerebral amyloid angiopathy or other small vessel disease pathology.
Department of Mental Health and Psychiatry, University Hospitals and University of Geneva, 2, chemin du Petit-Bel-Air, 1225, Geneva, Switzerland. eniko.kovari@hcuge.ch.
Enikö
E
Kövari
Massachusetts General Hospital Stroke Research Center, Harvard Medical School, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA. andreas.charidimou.09@alumni.ucl.ac.uk.
Andreas
A
Charidimou
Department of Internal Medicine, Rehabilitation and Geriatrics, University Hospitals and University of Geneva, 3 chemin du Pont-Bochet, 1226, Thônex, Switzerland. Francois.Herrmann@hcuge.ch.
François R
FR
Herrmann
Department of Mental Health and Psychiatry, University Hospitals and University of Geneva, 2, chemin du Petit-Bel-Air, 1225, Geneva, Switzerland. Panteleimon.Giannkopoulos@unige.ch.
Panteleimon
P
Giannakopoulos
Department of Mental Health and Psychiatry, University Hospitals and University of Geneva, 2, chemin du Petit-Bel-Air, 1225, Geneva, Switzerland. Constantin.Bouras@unige.ch.|Department of Internal Medicine, Rehabilitation and Geriatrics, University Hospitals and University of Geneva, 3 chemin du Pont-Bochet, 1226, Thônex, Switzerland. Constantin.Bouras@unige.ch.
Constantin
C
Bouras
Department of Internal Medicine, Rehabilitation and Geriatrics, University Hospitals and University of Geneva, 3 chemin du Pont-Bochet, 1226, Thônex, Switzerland. Gabriel.Gold@hcuge.ch.
Gabriel
G
Gold
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D066127:White Matter / Q000473:pathology
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins