Cloning of the presenilin 2 cDNA and its distribution in brain of the primate, Microcebus murinus: Coexpression with beta APP and tau proteins

A 1340-bp cDNA fragment encoding the lemurian presenilin 2 protein (PS2) wa s isolated from a Microcebus murinus brain cDNA library by PCR using oligon ucleotide primers based on the nucleotide sequence of the human gene. Analy sis of five isolated clones showed that the sequence encoded a 448-amino-ac id open reading frame, 95.5% identical to the human and 93.5% identical to the mouse presenilin 2 sequences. However, neither the localization of the 2 positions in PS2 nor that of the 43 positions in PS1 associated with earl y onset Alzheimer's disease were changed. Expression of the presenilin 2 wa s detected by RT-PCR and compared with that of presenilin I and beta APP in the brain and in peripheral tissues (liver, kidney, and spleen). Immunohis tochemistry with a specific polyclonal antiserum raised against a synthetic peptide from the N-terminal part of the human PS2 showed that the protein is distributed throughout the microcebe brain, in vascular and nerve struct ures. In cortical and in subcortical areas, PS2 labeling was weak and granu lar in appearance and was scattered throughout the cytoplasm of many neuron es, extending into neurites. The gene expression of PS2 increased with age but was not affected by the presence of numerous amyloid plaques. Double la beling immunocytochemistry detected very few neurones with combined immunor eactivity PS2 and APP, or PS2 and Tau. (C) 1998 Academic Press.