Matrix metalloproteinase-β19 expressed in cerebral amyloid angiopathy.
BACKGROUND
Cerebral amyloid angiopathy (CAA) is a frequent finding in the brains of patients with Alzheimer's disease (AD). CAA may be complicated with CAA-associated intracerebral haemorrhage (CAAH). Previous studies have revealed matrix metalloproteinase (MMP) expression in a mouse model of CAA and in human intracerebral haemorrhage. Here we studied the involvement of MMPs in human CAA and CAAH.


METHODS
To investigate the putative expression of MMPs in human CAA and CAAH (Step 1), immunohistochemistry (IHC) against MMPs-1, -2, -7, -9, -19 and -26 was applied on tissue microarray (TMA) constructed of cerebral samples from 29 individuals with AD, 15 with CAAH and 2 controls. The findings in TMA were confirmed (Step 2) in tissue samples from 64 individuals, 45 presenting with CAA (including 36 with CAAH) and 19 without CAA (including 11 with hypertensive cerebral haemorrhage).


RESULTS
In Step 1, immunoreactivity against MMPs-19 and -26 was detected in cerebral blood vessels in CAA. The results were confirmed in Step 2, where CAA (p<0.001) and intracerebral haemorrhage (p=0.045) were associated with vascular immunoreactivity against MMP-19. Multivariate analysis showed that the association between vascular MMP-19 and intracerebral haemorrhage was dependent from CAA. MMP-26 associated with CAA (p=0.021) but not with intracerebral haemorrhage.


CONCLUSIONS
This is the first human study showing local MMP-19 immunoreactivity in the Aβ-amyloid-laden blood vessels in CAA, suggesting that MMPs may be involved in CAA.
Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. maarit.tanskanen@helsinki.fi
Maarit
M
Tanskanen
Liisa
L
Myllykangas
Ulpu
U
Saarialho-Kere
Anders
A
Paetau
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000201:enzymology*; D001808:Blood Vessels / Q000201:enzymology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000201:enzymology*; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000209:etiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D046888:Tissue Array Analysis
D053505:Matrix Metalloproteinases, Secreted; C108362:matrix metalloproteinase 19