Decreased alternative splicing of estrogen receptor-α mRNA in the Alzheimer's disease brain.

In this study we identified 62 estrogen receptor alpha (ERα) mRNA splice variants in different human brain areas of Alzheimer's disease (AD) and control cases and classified them into 12 groups. Forty-eight of these splice forms were identified for the first time. The distribution of alternatively spliced ERα mRNAs was brain area- and case-specific. The dominant negative deletion (del.) 7 isoform appeared to be the major splice variant. The average number of ERα splice forms per brain area was lower in AD cases compared with controls, although the incidence of large deletions with alternative usage of 5' and 3' splice sites inside exons was more frequent in AD female cases. Relative transcription levels of del. 7 and del. 2 (missing exon 2) variants were decreased in the temporal cortex of AD patients, whereas the expression of the wild type ERα mRNA did not change. Our data show that alternative splicing of ERα mRNA is diminished in the AD brain and more prominently in AD female cases.