PMID- 2881207 OWN - NLM STAT- MEDLINE DCOM- 19870401 LR - 20240209 IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 325 IP - 6106 DP - 1987 Feb 19-25 TI - The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. PG - 733-6 AB - Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood vessels. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,500. The same polypeptide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome). We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor. FAU - Kang, J AU - Kang J FAU - Lemaire, H G AU - Lemaire HG FAU - Unterbeck, A AU - Unterbeck A FAU - Salbaum, J M AU - Salbaum JM FAU - Masters, C L AU - Masters CL FAU - Grzeschik, K H AU - Grzeschik KH FAU - Multhaup, G AU - Multhaup G FAU - Beyreuther, K AU - Beyreuther K FAU - Muller-Hill, B AU - Muller-Hill B LA - eng SI - GENBANK/Y00264 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Amyloid) RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Protein Precursors) RN - 0 (RNA, Messenger) RN - 9007-49-2 (DNA) SB - IM MH - Alzheimer Disease/*genetics MH - Amyloid/*genetics/metabolism MH - Amyloid beta-Peptides MH - Amyloid beta-Protein Precursor MH - Base Sequence MH - Brain/*metabolism MH - Brain Chemistry MH - Chromosomes, Human, Pair 21 MH - DNA/genetics MH - Down Syndrome/genetics MH - Fetus MH - Humans MH - Neurofibrils/analysis MH - Nucleic Acid Hybridization MH - Protein Precursors/*genetics/metabolism MH - Protein Processing, Post-Translational MH - RNA, Messenger/genetics EDAT- 1987/02/19 00:00 MHDA- 1987/02/19 00:01 CRDT- 1987/02/19 00:00 PHST- 1987/02/19 00:00 [pubmed] PHST- 1987/02/19 00:01 [medline] PHST- 1987/02/19 00:00 [entrez] AID - 10.1038/325733a0 [doi] PST - ppublish SO - Nature. 1987 Feb 19-25;325(6106):733-6. doi: 10.1038/325733a0.