The sample consists of 139 consecutive autopsies obtained over the 11-year span of 1997 to 2007. The 130 cases with bilateral hippocampi available for review comprise the sample in this study. In most cases (n = 121, = 93%), the entire extent of the hippocampus from pes to tail was evaluated by systematic sampling from four to seven consecutive 5-mm-thick blocks spanning the entire hippocampus. In nine cases, only two levels of the hippocampus were reviewed for one or both hemispheres:

at the level of the pes and the level of the lateral geniculate Inhibitors,research,lifescience,medical nucleus. HS was evaluated with the H&E stain (Fig. 1), where this lesion is characterized by severe loss of pyramidal neurons and accompanying gliosis. Severity of HS was scored as none, focal, or complete based on the extent of hippocampal involvement. HS was rated ‘none’ when there was no HS, ‘focal’ when HS was limited to a portion of a CA sector at a single level of the hippocampus, and ‘complete’ when HS involved the entire

pyramidal layer of CA1 and/or subiculum throughout the rostral–caudal extent of the hippocampus. Inhibitors,research,lifescience,medical Figure 1 (A) Low-power image of an H&E-stained section of an intact hippocampus with subfields indicated from a 91-year-old female. There is a full complement of neurons in all subfields. (B) Low-power image of an H&E-stained section from a 93-year-old … Standardized neuropathologic evaluation Cases were evaluated for neurofibrillary Inhibitors,research,lifescience,medical tangle load (Braak and Braak score), neuritic

plaque burden (CERAD rating), vascular brain injury Inhibitors,research,lifescience,medical including macroscopic-, lacunar-, and micro-infarcts (Selleck Alvocidib cerebrovascular parenchymal pathology scores (CVD-PS); Chui et al. 2006), and Lewy bodies (McKeith Lewy body score; McKeith et al. 1996). Blood vessels were rated for severity of cerebral amyloid angiopathy (Vonsattel rating [grade 0 to III, expanded to grade IV where there Inhibitors,research,lifescience,medical is evidence of CAA-associated microangiopathy]; Vinters and Vonsattel 2001). In this study, cases were categorized as AD if the Braak and Braak score was ≥V. IVD was operationally defined as CVD-PS score ≥20; diffuse Lewy body disease (DLBD) as Lewy Body score ≥3. A diagnosis of FTLD was based on a consensus between two board-certified neuropathologists below using criteria which included a pattern of atrophy consistent with FTLD, confirmed by appropriate microscopic findings. Immunohistochemistry TDP-43 immunostaining was carried out bilaterally on a subset of cases (n = 45) representing normal hippocampus (seven cases), IVD without HS (six cases), AD without HS (18 cases), and HS with and without comorbidities (14 cases). Ten-micron-thick sections of formalin-fixed, paraffin embedded tissue from hippocampus were immunostained for TDP-43 (Proteintech Group, Chicago, IL, 1:50 dilution). The slides were treated with 10 mmol/L sodium citrate pH 4.5 for 10 min at 98°C, prior to overnight incubation with the primary antibody at 4°C.