Biological correlates of clinical heterogeneity in primary dementia

While there is considerable variation in the clinical expression of Alzheimer's disease (AD), the determinants of this clinical heterogeneity remain unclear. Platelet membrane fluidity (PMF) identifies a subgroup of patients with AD with distinct clinical features that appear to be genetically determined. Results from an integrated series of studies suggest a cellular substrate for the increase in PMF associated with this clinical subgroup, and a model for the participation of the PMF locus in the pathophysiology of AD is proposed. In addition to this approach, studies of the neuropathologic and neurochemical determinants of major depression and psychosis in the context of primary dementia are presented. The results may explain the different prognoses associated with these behavioral syndromes in patients with AD, as well as the symptoms of the syndromes themselves.