Premium
Altered Expression of Amyloid β Precursor mRNAs in Cerebral Vessels, Meninges, and Choroid Plexus in Alzheimer's Disease a
Author(s) -
PREMKUMAR D. R. D.,
KALARIA R. N.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb34434.x
Subject(s) - choroid plexus , gene isoform , meninges , pathology , biology , amyloid precursor protein , alzheimer's disease , senile plaques , cerebral cortex , cerebral amyloid angiopathy , central nervous system , endocrinology , gene , medicine , disease , biochemistry , dementia
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 Aβ 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 Aβ transcripts encoding the Aβ 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 Aβ 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 Aβ in cerebrovascular tissues in AD.