Neruobiology of Posterior Cortical Atrophy

 
   Lead Investigator:    Juan Troncoso
   Institution      :    John Hopkins
   E-Mail           :    troncoso@jhmi.edu
   Proposal ID      :    1551



   Proposal Description:
   We are requesting from NACC information on availability of autopsy cases of PCA for the proposal delineated below. Studies will be conducted in a collaborative fashion with colleagues at the referring Alzheimer?s Disease Centers (ADCs)  We are seeking information about the availability of autopsy tissue from cases with a clinical diagnosis of PCA, because these cases are quite rare and we need a sufficient sample size in order to conduct the proposed study. PCA is a form of progressive dementia characterized by early impairments of high visual function. As first reported by Benson et al. ( Arch Neurol.  1988 45:789-793 ), these impairments include alexia, agraphia, visual agnosia, and components of Balint's, Gerstmann's, and transcortical sensory aphasia syndromes. Later in the course of the disease, memory, insight, and judgment disorders become manifest. The onset of PCA clinical manifestations is usually before 65 years of age. The predominant morphological feature of PCA is atrophy of the occipital and parietal regions as demonstrated by imaging and postmortem examination. The histopathology of this entity is heterogeneous, with cases of Alzheimer?s disease, Lewy body disease, and prions. (S. J. Crutch et al. Lancet Neurology 2012, 11:170-178).  In this proposal, our goal is to examine the gene expression of relevant cortical regions in autopsy cases of PCA compared with cases of AD dementia of a comparable age with a more typical presentation, and correlate these findings with histopathological features and clinical histories. We propose to use tools that allow single cell expression assessment from neurons, astrocytes, and microglia. This component of the study will be conducted by Dr. Scholz in collaboration with Drs. Ted and Valina Dawson (JHU). Histological examination will be performed in the laboratory of Dr. J. Troncoso and include silver stains (Hirano) and immunohistochemistry for A-beta, phospho tau, alpha-synuclein, TDP-43, and IBA1 (microglia). Cli