S1‐02‐03: Innate immune pathology in Alzheimer's disease

not available. S1-02-04 MICROVASCULAR PATHOLOGY IN ALZHEIMER’S DISEASE: BRAIN REGIONAL ANALYSES OF CAPILLARY NETWORKS Karen M. Cullen, The University of Sydney, Sydney, NSW, Australia. Contact e-mail: kcullen@anatomy.usyd.edu.au Background: Evidence of a substantial vascular component to the pathogenesis Alzheimer’s disease (AD) has converged from multiple sources, among these in vivo, epidemiologic and clinicopathologic studies. It is becoming increasingly evident that cerebrovascular pathology is not simply an add-on to classic AD pathology but a driving force in development of key lesions. We recently reported the presence of multiple small haemorrhages in the brains of AD patients. These haemorrhages coincide with amyloid deposits and encircle microvessels, mainly capillaries. Methods: In post mortem tissue from cases with a broad range of AD lesion burden, we investigated the location of microvascular anomalies along the three dimensional cortical and subcortical capillary networks. Immunihistochemical labelling of the endothelium, smooth muscle and pericapillary cells were used in combination with markers for amyloid and tau epitopes, haemorrhage and inflammation on 50-300mm sections of cortex, medial temporal lobe, brainstem, cerebellum, and basal forebrain. Vessel density and morphology were characterised quantitatively and qualitatively for each region. The location of lesions along the network was assessed. Results: The morphology (length density, branching pattern, curvature and distance to feeding artery) of the microvasculature is highly specific to brain region. Capillary ruptures were most common in highly branched networks and almost exclusively in cell-dense areas where capillary density is greatest. In a subset of patients, microvascular damage appeared along straight lengths of vessels in both grey and white matter. Capillary damage was more frequent adjacent to bifurcations. Importantly, early signs of neuritic pathology was seen perivascularly, coincident with foci of phagocytic microglia. The clusters of lesions could be traced to feeding or draining vessels. Conclusions: Analysis of the capillary provides insight into the differential vulnerability of brain regions in AD and the anatomical relationship between Aß deposits and tau pathology. The positioning of capillary anomalies near stress points and clustered upor down-stream from supplying or draining vessels suggest that multiple, likely additive, factors contribute to weakness in the endothelial barrier. The antecedent causes of capillary degeneration deserve focus in ongoing efforts to reduce the prevalence of AD. S1-02-05 REPRODUCIBILITY IN THE ASSESSMENT OF ALZHEIMER’S DISEASE AND LEWY BODY DISEASE-RELATED PATHOLOGIES: A STUDY BY BRAIN NET EUROPE Irina I. Alafuzoff, Uppsala University, Uppsala, Sweden. Contact e-mail: irina.alafuzoff@genpat.uu.se Background: When dealing with neurodegenerative disorders assessment of proteins such as hyperphosphorylated-tau (HP-tau), b-amyloid (bA) and a-synuclein (aS) are carried out. Furthermore, it is not sufficient to merely assess the presence of these proteins but in addition to investigate their regional distribution. The regional distribution of the pathologies listed above has been shown to be in some extent regular and several strategies such as the staging of Alzheimer’s disease (AD) related HP-tau, phase assessment of ADrelated Ab and the staging/ typing of Lewy Body (LB)-related aS-pathology has been produced. Methods: The BrainNet Europe (BNE) consortium gives an excellent platform to test the reliability and reproducibility of these published strategies and to identify possible weaknesses and pitfalls. Thus, when needed alterations/modification can be made to the original instructions to reach a high reproducibility. During the last years, BNE consortium has assessed the inter-rater variability of the pathologies listed above. More than 20 neuropathologists/observers participated in each trial. Results: Regarding the staging of AD-related HP-tau pathology a high agreement can be reach in an interlaboratory setting but only in cases with moderate to severe involvement. Particularly, cases with mild involvement yielded poor results. Regarding the assessment of regional distribution of Ab and aS, the inter-rater variability was lower and the results thus better. Regarding the staging/typing of LB-related aSpathology, some modifications to the original instructions had to be made to reach low inter-rater variability. Conclusions: The results of the BNE consortium indicate that simple and clear operationalized criteria yield high agreement rates. S1-02-06 PRIMARY NEUROPATHOLOGIC DIAGNOSIS AND CO-OCCURRENCE OF OTHER NEUROPATHOLOGIC FEATURES: RESULTS FROM THE NATIONAL ALZHEIMER’S COORDINATING CENTER (NACC) Walter A. Kukull, Leslie Philips, Dawn Gill, Joylee Wu, Michael Sachs, Duane Beekly, Thomas Koepsell, University of Washington, Seattle, WA, USA; University of Washington, Seattle, WA, USA. Contact e-mail: kukull@u.washington.edu Background: Alzheimer’s disease (AD) and similar dementia-causing disorders are defined at autopsy, primarily by the occurrence and location of specific pathologic features. Co-occurrence of other neuropathologic