Amyloid beta protein (Abeta) deposition was investigated in the frontal cortex of 54 autopsy cases of frontotemporal lobar degeneration (FTLD) using methenamine silver staining, and immunohistochemistry employing the monoclonal end-specific antibodies BC05 and BA27 to visualize deposits containing Abeta(42(43)) and Abeta(40), respectively. Abeta was detected in 14 (26%) patients, nearly always in the form of diffuse Abeta(42(43)) containing plaques though some cored, neuritic plaques with trace amounts of Abeta(40) were occasionally seen. The 14 patients showing Abeta deposits were significantly older at onset of illness than those 40 patients without Abeta. It was only possible to genotype 46/54 cases, 16 of whom bore at least one copy of the Apolipoprotein E (APOE) epsilon4 allele, giving an allele frequency of 20%. Possession of APOE epsilon4 allele was significantly associated with deposition of Abeta such that 10/16 epsilon4 allele bearers had Abeta deposits. Eight of these ten patients showed only mild to moderate amounts of Abeta, but in two patients, one homozygous and one heterozygous for epsilon4 allele, there was extensive neuritic plaque and neurofibrillary tangle formation. In contrast, only few non-epsilon4 allele bearers (4/30) showed minor Abeta deposits. When stratifying for APOE epsilon4 allele, both bearers and non-bearers of epsilon4 allele with Abeta deposits had a significantly later age at onset than their respective groups without Abeta deposits. We conclude that the likelihood of Abeta deposition, as a secondary and coincidental feature unrelated to the primary pathological process, within the brains of individuals with FTLD will be high if patients have a sufficiently late onset of illness or happen to be a bearer of the APOE epsilon4 allele. Indeed 9/14 patients with Abeta deposits studied here had an onset of illness after 55 years of age and bore APOE epsilon4 allele.