Proteolytic fragments of Alzheimer's disease-associated presenilin 1 are present in synaptic organelles and growth cone membranes of rat brain

Previous studies have demonstrated the molecular linkage of three causative genes for early-onset Alzheimer's disease: the presenilin 1 gene on chromo some 14, the presenilin 2 gene on chromosome 1, and the amyloid precursor p rotein gene on chromosome 21, In the present study, we have investigated th e distributions of the similar to 20-kDa C-terminal and similar to 30-kDa N -terminal fragments of presenilin 1 and the amyloid precursor protein in ra t brain and compared them with the distribution of several marker proteins. The fragments of presenilin 1 are present in synaptic plasma membranes, ne urite growth cone membranes, and small synaptic vesicles of rat brain. Both proteolytic fragments are coenriched in the corresponding tissue fractions . Based on this observation, it seems likely that N- and G-terminal preseni lin 1 fragments form a functional unit while remaining associated. in contr ast to a predominant subcellular localization of presenilin 1 to the endopl asmic reticulum and Golgi apparatus in different cell lines, our results in dicate that rat brain presenilin 1 fragments exit from these biosynthetic c ompartments to reach synaptic organelles in neurons.