is a member of evolutionarily conserved protein family. In 1987, first time APP
cDNA was sequenced in human brain tissue (Kang,
Lemaire et al. 1987). A large number of APP family
members were identified in a variety of mammalian as well as non-mammalian tissues.
The APP family includes APP, the APP-like protein-1 (APLP1) and the APP-like
protein-2 (APLP2) (Wasco,
Bupp et al. 1992; Wasco, Gurubhagavatula et al. 1993). In humans, the APP gene is
located on chromosome 21 (21q21.3). It contains 18 exons with 240 kb nuceotides
Sasaki et al. 1990). App gene exhibits
constitutive expression. The promoter of APP gene unlike others lacks typical protein
binding domain CAAT and TATA boxes. It has some consensus sequences known as a heat
shock control element, SP1, AP1, AP4 and Alu type repetitive sequences which are
crucial for binding with proteins for transcription (Salbaum,
Weidemann et al. 1988; Izumi, Yamada et al. 1992; Quitschke and Goldgaber 1992). The SP1, AP1 and AP4 sequence containing
promoter are involved in expression of protein during cell proliferation and differentiation.
During neurite growth and synapse formation, the expression of APP and other APP
like proteins increase (Clarris,
Key et al. 1995).
transcription, alternative splicing of APP mRNA can result in a number of APP
splice variants (Figure. 3.3). The major expressed isoforms of APP are 770, 751
or 695 amino acid residues long which are written as APP770, APP751 and APP695
respectively (Figure-4.3). The APP751 and APP695 isoforms are produced as a
result of exclusion of exons 7 and/or 8 (Kang,
Lemaire et al. 1987; Tanzi, McClatchey et al. 1988; Weidemann, Konig et al.
1989). Some uncommon splice variants are
also reported, such as L-APP, which lacks exon 15 and APP639, which lacks exons
2, 7 and 8 (Tang,
Wang et al. 2003).
4.3- Amyloid precursor protein (APP) gene and mRNA variant. (A)APP gene consisting of 18
exons is located on chromosome 21q21.3. (B) Alternative splicing of mRNA
forms three isoforms APP695, APP751 and APP770. APP770 isoform is formed
by joining of all the 18 exons. Exclusion of 7th and 7th-8th
exons through alternative splicing form isoforms APP751 and APP695.
APP mRNA is expressed in a broad range of tissues including immune system
(thymus, spleen), the nervous