GENETIC-STUDIES IN ALZHEIMERS-DISEASE WITH AN NACP ALPHA-SYNUCLEIN POLYMORPHISM/

The non-A beta component of Alzheimer's disease amyloid (NAC) is copur ified with amyloid from the brain tissue of Alzheimer's disease victim s and is immunohistochemically localized to amyloid fibrils. NAC is a hydrophobic peptide fragment from the NAC precursor protein (NACP/alph a-synuclein) that is localized to presynaptic terminals. We used a pol ymorphic dinucleotide repeat sequence in a genomic clone of NACP for g enetic association and linkage studies. Screening of Alzheimer's disea se families failed to establish linkage between NACP and Alzheimer's d isease. Nevertheless, one of the NACP polymorphisms (NACP allele 2) wa s shown to have significant association with healthy elderly control i ndividuals with apolipoprotein E risk. This may indicate a possible pr otective function of the allele.