purified a protein derived from the

purified a protein derived from the twisted beta-pleated sheet fibrils present in cerebrovascular amyloidoses and in the amyloid plaques associated with Alzheimer disease (AD; 104300). The 4.2-kD polypeptide was called the 'beta-amyloid protein' because of its partial beta-pleated sheet structure. The proteins from both disorders have an identical 28-amino acid sequence.

Masters et al. (1985) purified and characterized the cerebral amyloid protein that forms the amyloid plaque core in Alzheimer disease and in older persons with Down syndrome (190685). The protein consists of multimeric aggregates of a 40-residue polypeptide with a molecular mass of approximately 4 kD. The amino acid composition, molecular mass, and NH2-terminal sequence of this amyloid protein were found to be almost identical to those described for the amyloid deposited in the congophilic angiopathy of Alzheimer disease and Down syndrome.

Robakis et al. (1987) isolated clones corresponding to the APP gene from a human brain cDNA library. The deduced 412-residue protein contains the 28-amino acid sequence of the beta-protein located near the C terminus, suggesting that the beta-protein is cleaved posttranslationally from a larger precursor. RNA blot analysis detected a 3.3-kb mRNA transcript in brains from a normal individual, an AD patient, and a patient with Down syndrome. Tanzi et al. (1987) isolated a cDNA corresponding to the beta-amyloid protein and concluded that it is derived from a larger protein expressed in a variety of tissues.

Kang et al. (1987) isolated and sequenced an apparently full-length cDNA clone coding for the APP A4 polypeptide, a designation they used for the major protein subunit of the amyloid fibril of tangles, plaques, and blood vessel deposits in AD and Down syndrome. The predicted 695-residue precursor contains features characteristic of glycosylated integral membrane cell surface receptor proteins. Beta-amyloid, the principal component of extracellular deposits in senile plaques, is a cleavage product of the larger precursor and encompasses 28 amino acids of the ectodomain and 11 to 14 amino acids of the transmembrane domain. Kang et al. (1987) noted that this protein shows similarities to the prion protein (PRNP; 176640) found in the amyloid of transmissible spongiform encephalopathies (Oesch et al., 1985). Membrane-spanning domains of both proteins may share an amyloid-forming or amyloid-inducing potential.

Goldgaber et al. (1987) found that a 3.5-kb APP mRNA was detectable in mammalian brains and human thymus. The gene was found to be highly conserved in evolution.

Ponte et al. (1988), Tanzi et al. (1988), and Kitaguchi et al. (1988) showed that the amyloid protein precursor contains a domain very similar to the Kunitz family of serine protease inhibitors. All 3 groups found the variable presence of a 56-residue domain interpolated at residue 289 within the proposed extracellular portion of the amyloid precursor protein. The newly found amyloid protein sequence was 50% identical to bovine pancreatic trypsin inhibitor, also called aprotinin, and to the second inhibitory domain of a human plasma protein, inter-alpha-trypsin inhibitor.

Van Nostrand et al. (1989) presented evidence that protease nexin-II (PN2), a protease inhibitor that is synthesized and secreted by various cultured extravascular cells, is identical to APP.

Alternative splicing of transcripts from the single APP gene results in several isoforms of the gene product, of which APP695 is preferentially expressed in neuronal tissues (Sandbrink et al., 1994).

Results (Indonesian) 2:

dimurnikan protein yang berasal dari beta-lipit fibril lembar memutar hadir dalam amyloidoses serebrovaskular dan dalam plak amiloid yang berhubungan dengan penyakit Alzheimer (AD; 104300). The 4.2-kD polipeptida disebut 'protein beta-amyloid' karena struktur lembaran beta-lipit parsial. Protein dari kedua gangguan memiliki urutan asam 28-amino identik.

Masters et al. (1985) dimurnikan dan ditandai protein amiloid serebral yang membentuk amiloid plak inti dalam penyakit Alzheimer dan pada orang yang lebih tua dengan sindrom Down (190.685). Protein terdiri dari agregat multimeric dari polipeptida 40-residu dengan massa molekul sekitar 4 kD. Komposisi asam amino, massa molekul, dan urutan NH2-terminal protein amiloid ini ditemukan hampir identik dengan yang dijelaskan untuk amiloid disimpan di angiopati congophilic penyakit Alzheimer dan sindrom Down.

Robakis et al. (1987) klon terisolasi sesuai dengan gen APP dari perpustakaan cDNA otak manusia. Menyimpulkan protein 412-residu berisi urutan asam 28-amino dari beta-protein terletak di dekat terminal C, menunjukkan bahwa beta-protein dibelah pascatranslasi dari prekursor yang lebih besar. Analisis RNA blot mendeteksi 3.3-kb mRNA transkrip dalam otak dari individu normal, pasien AD, dan pasien dengan sindrom Down. Tanzi et al. (1987) mengisolasi cDNA sesuai dengan protein beta-amyloid dan menyimpulkan bahwa itu berasal dari protein yang lebih besar dinyatakan dalam berbagai jaringan.

Kang et al. (1987) terisolasi dan sequencing sebuah tampaknya full-length cDNA clone coding untuk polipeptida APP A4, sebutan mereka digunakan untuk subunit protein utama dari fibril amiloid dari kusut, plak, dan deposit pembuluh darah di AD dan sindrom Down. Diprediksi prekursor 695-residu mengandung fitur karakteristik glikosilasi terpisahkan protein reseptor permukaan sel membran. Beta-amyloid, komponen utama dari deposito ekstraseluler pada plak pikun, adalah produk pembelahan prekursor yang lebih besar dan mencakup 28 asam amino dari ectodomain dan 11 sampai 14 asam amino dari domain transmembran. Kang et al. (1987) mencatat bahwa protein ini menunjukkan kesamaan dengan protein prion (PRNP; 176.640) ditemukan di amiloid dari encephalopathies spongiform menular (Oesch et al, 1985.). Domain yang membentuk membran dari kedua protein dapat berbagi amyloid pembentuk atau potensial amiloid-inducing.

Goldgaber et al. (1987) menemukan bahwa 3,5-kb APP mRNA terdeteksi di otak mamalia dan timus manusia. Gen itu ditemukan sangat kekal dalam evolusi.

Ponte et al. (1988), Tanzi et al. (1988), dan Kitaguchi et al. (1988) menunjukkan bahwa prekursor protein amyloid mengandung domain yang sangat mirip dengan keluarga Kunitz serin protease inhibitor. Semua 3 kelompok ditemukan adanya variabel dari domain 56-residu diinterpolasi pada residu 289 dalam bagian ekstraseluler diusulkan dari protein prekursor amiloid. Urutan protein amyloid yang baru ditemukan adalah 50% identik dengan sapi inhibitor tripsin pankreas, juga disebut aprotinin, dan untuk domain penghambatan kedua dari protein plasma manusia, antar-alpha-tripsin inhibitor.

Van Nostrand et al. (1989) disajikan bukti bahwa protease nexin-II (Pn2), protease inhibitor yang disintesis dan disekresi oleh berbagai sel ekstravaskular berbudaya, identik dengan APP.

Splicing alternatif transkrip dari APP hasil gen tunggal dalam beberapa isoform dari produk gen , yang APP695 yang istimewa disajikan dalam jaringan saraf (Sandbrink et al., 1994).