ALTERATION IN BRAIN PRESENILIN-1 MESSENGER-RNA EXPRESSION IN EARLY-ONSET FAMILIAL ALZHEIMERS-DISEASE

The expression of the presenilin 1 (PS-1) gene has been investigated b y in situ hybridization in early onset familial Alzheimer's disease (F AD), late onset Alzheimer's disease (AD) and normal control brain. Mut ations in this gene are responsible for chromosome 14-linked FAD. We h ave found that presenilin 1 mRNA is present throughout the human brain with a distribution consistent with both a glial and neuronal localiz ation. The in situ hybridization pattern was similar for the controls, the early onset FAD cases and the late onset AD cases. However, one o f the two forms of the mRNA for PS-1, the long form (which contains a sequence encoding a four amino acid (VRSQ) insert at its 5' end) was s ignificantly reduced in early onset FAD brain compared with late onset AD. We suggest that this long transcript may alter the normal pathway for processing of amyloid precursor protein, the protein which appear s to be central in the pathogenesis of AD. (C) 1996 Academic Press Lim ited