Primary degenerative dementia is a major mental health problem in the aging population. The PEF locus appears to be an important genetic determinant of clinical heterogeneity in this patient group. Initial evidence suggests that the PEF locus may reside on chromosome 21. A genetic mapping strategy is proposed to localize the PEF locus, toward an understanding of the function of this gene and its role in the pathophysiology of mental disorders of late life.