Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.

Abstract:

:Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6-9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA.

journal_name

Nature

journal_title

Nature

authors

Tanzi RE,McClatchey AI,Lamperti ED,Villa-Komaroff L,Gusella JF,Neve RL

doi

10.1038/331528a0

subject

Has Abstract

pub_date

1988-02-11 00:00:00

pages

528-30

issue

6156

eissn

0028-0836

issn

1476-4687

journal_volume

331

pub_type

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