P2-195: Semantic dementia: Reflections of a French working group for diagnosis criteria and constitution of a cohort of patients

Abstract

diagnosed by clinical symptoms, its neuropathological diagnosis can include Pick’s disease, frontotemporal dementia and Alzheimer’s disease. However, it is still unclear what causes the focal neuropathological changes in PPA. To address this question, we performed microarray study on four PPA cases with FTD and three aged control cases. Methods: RNA samples were extracted and purified from homogenate of one-side angular gyrus and occipital lobe from each case using Absolutely RNA RT-PCR Miniprep Kit (Stratagene), then were hybridized to the GeneChip Human Whole Genome U133 plus 2.0 Array (Affymetrix). Results were screened for probes that were significantly different from one group to another with p-value less than 0.05 for intensities over background level, high signal/ noise ratio and a fold change more than 2. Results: Among 47,000 available probes, 118 probes were upregulated and 44 were downregulated in angular gyrus of PPA compared to that of control cases, and 91 upregulated and 24 downregulated genes are selected in angular gyrus compared to occipital lobes in PPA. Functional analysis of both data sets showed that complement pathways were significantly upregulated in angular gyrus of PPA cases. Gene set enrichment analysis supported this expression change of complement pathways. To further examine this upregulation in angular gyrus, we immunostained paraffin sections of identical cases with antibodies against C1q, showing that C1q-immunoreactivites were detected dominantly in angular gyrus of PPA cases comparing to that of control cases or occipital lobe of PPA. Three of four PPA cases had a lot of C1q-positive spiral structures in white matter of angular, which were never seen in control cases or Alzheimer disease cases. Conclusions: Our study suggests that significant upregulation of complement pathways in angular gyrus, especially in white matter, is strongly related to PPA. We postulate that suppression of upregulated complement pathways may lead to the therapy of PPA.