Abstract:
:Altered tissue-specific processing or production of the amyloid precursor protein (APP) is thought to be central to amyloid deposition in cerebrovascular and the neocortical tissues in Alzheimer's disease (AD). We demonstrate that A beta peptide(s) is readily detectable and increased in cerebral vessels, meninges and choroid plexus obtained at autopsy from AD subjects compared to age-matched controls. Using the reverse transcription (RT)-polymerase chain reaction (PCR), we further found that A beta transcripts encoding the A beta sequence in all forms of APP containing exons 16 and 17 (of APP770) were significantly increased in vessel samples in AD subjects. This was also evident in the neocortical samples and not related to pre-mortem factors or postmortem interval. It is possible that the increased A beta mRNAs reflect enhanced expression of the L-APP isoform (APP770 without exon 15) expressed in leukocytes and glia alike. We also found evidence for changed proportions of APP 770, 756 and 695 mRNAs in cerebral vessel samples from AD subjects compared to controls. Whereas APP770 and APP751, the predominant forms, were significantly decreased, APP695 transcript was increased in vessel samples from AD subjects. Such changes were not evident in neocortical samples from the same subjects. These observations suggest tissue-specific changes in expression of APP isoforms implicating one of the mechanisms for increased accumulation of A beta in cerebrovascular tissues in AD.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Premkumar DR,Kalaria RNdoi
10.1111/j.1749-6632.1996.tb34434.xsubject
Has Abstractpub_date
1996-01-17 00:00:00pages
288-92eissn
0077-8923issn
1749-6632journal_volume
777pub_type
杂志文章abstract::Few studies have evaluated the impact of nutritional supplementation among pregnant adolescents. We examined the effects of the Rang Din Nutrition Study (RDNS) interventions on children born to mothers <20 years of age. The RDNS was a cluster-randomized effectiveness trial with four arms: (1) women and children both r...
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journal_title:Annals of the New York Academy of Sciences
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