Presenilin-1 exists in the axoplasm fraction in the brains of aged Down's syndrome subjects and non-demented individuals.

Abstract Missense mutations in the presenilin-1 (PS-1) gene are known to be responsible for early-onset familial Alzheimer's disease (AD). The normal physiological functions of PS-1 are still incompletely understood, although data on the intracellular localization of PS-1 are accumulating, indicating that it exists mainly in endoplasmic reticulum and Golgi compartments. To investigate the localization and functions of PS-1 in the human brain, we separated axoplasm fractions from the cerebral white matter of Down's syndrome (DS) subjects with AD pathology and non-demented individuals using the axonal flotation method, and analyzed them immunocytochemically. All axoplasm fractions contained the 28–34 kDa amino-terminal fragment and the18 kDa carboxy-terminal fragment of PS-1, although there was no specific abnormality of this protein in the DS brains with AD pathology. This finding indicates that there is intracellular trafficking of PS-1 through the axons in the human brain, and thus provides new information about the physiology of PS-1.