Such observations are consistent with previous reports where a relatively high APOE ε4 allele frequency was also found among AD (and DLB) cases with capillary involvement compared with those without capillary involvement [11, 14, 22, 23]. The type 4 phenotype was regarded as the CAA-predominant phenotype in which a heavy Aβ deposition was observed in leptomeningeal vessels, Apoptosis inhibitor cortical vessels and capillaries with abundant perivascular deposition of Aβ (dyshoric change). Plaques were either absent or relatively sparse. This phenotype was observed in four (3%) patients,

where at least one region (occipital cortex, but usually all three regions) of the brain was involved. Other workers have reported similar cases, and termed them the ‘vascular variant of Alzheimer’s disease’ or ‘sporadic amyloid angiopathy’. A similar pathology has been described in inherited forms of AD associated with APP692 (Flemish) mutation where Aβ

deposition was referred to as ‘vasculocentric’ [24]. Vidal et al. [25] reported on two sporadic AD cases, both homozygous for APOE ε4 allele, Talazoparib cell line without mutations in APP or PSEN-1 genes, whose main pathological feature was diffuse amyloid angiopathy without evidence of SP. They hypothesized that APOE ε4 allele homozygosity could have been a contributing factor favouring vascular amyloid deposition in leptomeningeal and cortical vessels. APOE genotypes were only available for three of the patients in our cohort, two were APOE ε4 allele carriers (one being APOE ε4 homozygous and one being heterozygous), but the other was a non-APOE ε4-allele carrier (APOE ε3/ε3). Therefore, it cannot be presumed that APOE ε4 allele homozygosity is the sole driving force underlying this phenotype. Interestingly, while the clinical phenotype was available for only one of the present type 4 cases (‘memory’ predominant), SPTLC1 one of the other patients had been diagnosed with Frontotemporal

dementia, and thereby was likely to have presented as the ‘frontal’ variant of AD. Vidal et al. [25] further reported that both of their patients had markedly impaired short term verbal recall memory. It is possible therefore that the type 4 pathological phenotype may be more associated with a focal variant of AD, than presenting as ‘typical’ AD. Curiously comparisons of plaque density across the four phenotypes failed to bear out visual impressions of a difference between this group and the other three groups. This is probably due to the low number of type 4 cases available for analysis. Although Thal et al. [11] reported an increased frequency of APOE ε2 allele among their type 2 compared with type 1 (our type 3), CAA cases, we were unable to formally demonstrate such an association in the present study, probably due to the small number of cases of any histological type possessing APOE ε2 allele.