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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-1-30
pubmed:abstractText
Mutations within the Abeta sequence of the AbetaPP gene are associated with familial forms of cerebral amyloid angiopathy (CAA). One mutation, Abeta D23N, was identified in a family in Iowa with a clinical history of early-onset dementia. We analyzed the pattern of Abeta deposition in the hippocampus of an individual with Iowa CAA. In addition to strong amyloid angiopathy, we found unusual diffuse Abeta deposits in the CA4, and in the parenchyma near amyloid-laden vessels. ELISA of cortical brain extracts showed that Abeta40 was nearly 20-fold higher than Abeta42, in both soluble and insoluble fractions. We identified an Abeta antibody that recognized wild-type Abeta but not Iowa Abeta. With this antibody, we found that wild-type Abeta was present in the Abeta deposits, but limited to the strongest deposits in the cerebrovasculature. Previous in vitro studies suggested that the presence of an asparagine at position 23 of Abeta favored formation of an isoAsp residue, which was associated with increased Abeta fibrillogenesis. Using isoAsp-specific antibodies in immunohistochemical studies, we examined the distribution of isoAsp Abeta in the Iowa brain. IsoAsp7 Abeta was present in both the parenchymal and vascular deposits, whereas isoAsp23 Abeta was present only in vascular deposits. These data suggest that alteration of Abeta Asn23 to isoAsp may be an important determinant in the deposition of Abeta in cerebral blood vessels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0001-6322
pubmed:author
pubmed:issnType
Print
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
252-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Abeta species, including IsoAsp23 Abeta, in Iowa-type familial cerebral amyloid angiopathy.
pubmed:affiliation
Alzheimer Research Unit, Massachusetts General Hospital, 114 16th St., Charlestown 02129, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.