The ‘typical’ presentation describes the majority of patients with AD who suffer a broad spectrum of clinical symptoms characterized by early episodic memory loss followed by a combination of attention-executive, language and visuospatial impairments. The ‘focal’ presentations describes those cases where one aspect of brain function (cognition) declines

disproportionately to the others. The focal presentations could be subtyped further into a ‘memory (amnestic)’ variant (n = 6), ‘frontal’ variant (n = 3), ‘visual’ variant (n = 3) and a ‘language’ variant (n = 5). Because of the small number of subtypes available, however, it was only possible to assess whether the distribution of ‘typical’ or ‘focal’ presentations differed Metformin in vitro among the pathological phenotypes. APOE genotyping from DNA extracted from frozen brain tissue (cerebellum or frontal cortex) by phenol chloroform had been previously performed on 127 cases, according to method of Wenham et al. [13]. Sections of frontal (Brodmann areas 8/9), temporal cortex (Brodmann areas 21/22 to include hippocampus) and occipital cortex (Brodmann areas 17/18) were cut at 6 μm thickness from formalin fixed, paraffin embedded blocks and mounted on to glass slides. Sections were first hydrated through successive baths of xylene, alcohols

of decreasing concentration find more and distilled water. The rehydrated sections were transferred to a ceramic holder and subject to chemical antigen retrieval with 90% formic acid at room temperature for 20 min. Sections were incubated for 30 min at room temperature in 0.3% peroxide in methanol to quench endogenous peroxidise activity, and then for a further 30 min at room temperature in Vectastain Elite PK-6100 horse serum as blocking buffer. Sections were then incubated for 1 h at room temperature in mouse monoclonal antibody directed against Amyloid-β17–24 (4G8) (Signet Labs Inc., Dedham, MA, USA), which recognizes D-malate dehydrogenase all molecular forms of

Aβ, at a concentration of 1:3000. The sections were incubated for 30 min in a biotinylated secondary antibody followed by 30 min in avidin–biotin complex (ABC) reagent (both Vectastain Elite PK-6100 Mouse IgG), both at room temperature. Sites of immunoreactions were visualized by incubating in DAB (3,3′-diaminobenzidine tetrahydrochloride) for 5 min, followed by light counterstaining with haematoxylin (Vector H-3401). Sections were dehydrated and mounted for analysis under the microscope. The histological sections were examined under a Leica DMR light microscope. All assessments were made by a single observer (NA). The three topographical regions (frontal, temporal, occipital) for each case were scored consecutively (see below). Sections were scored twice to increase objectivity, and any discrepancies reconciled by consultation with a second observer (D.M.A.M.). The system used to grade CAA was similar to that originated by Olichney et al.