S1‐04–05: Genetics of human memory

not available. SUNDAY, JULY 27, 2008 ORAL O1-01 DIAGNOSIS AND CLINICAL COURSE: MOLECULAR PATHOLOGY AND HISTOPATHOLOGY 1 O1-01-01 STRUCTURAL CORRELATE OF PROGRESSIVE APHASIA IN ALZHEIMER’S DISEASE David G. Munoz, John Woulfe, Andrew Kertesz, University of Toronto, Toronto, ON, Canada; University of Ottawa, Ottawa, ON, Canada; University of Western Ontario, London, ON, Canada. Contact e-mail: dave_munoz@yahoo.com Background: Some patients who eventually receive a pathological diagnosis of Alzheimer’s disease (AD) present with prominent language difficulties at onset. The pathologic basis of this atypical clinical course is not known, and we aimed to determine whether it was associated with variations in the plaque and tangle load, or the presence of different lesions. Methods: The brains of all eight patients (M:F 4:4) examined at the Cognitive Neurology Clinic of the University of Western Ontario who presented with episodic memory difficulties in addition to severe language impairment at the onset of disease (average 67.8 5.5 yrs) and had an autopsy (average 76.7 4.8 yrs) were assessed histologically by means of Bielschowsky and Gallyas silver stains and tau immunostains using conformation-dependent (tau-2) and phosphorylation dependent (AT8) antibodies. A group of six patients with a clinical diagnosis of probable AD and classical clinical presentation were used for comparison. Results: The plaque and tangle load placed all patients in the “high likelihood that the dementia was due to AD” category by the NIA-Reagan criteria. The load was not increased in language-related areas and there were no significant infarcts. Seven of the language-impaired patients, but none of the comparison group showed in addition large argyrophilic thorny astrocyte clusters (ATAC) in cortex and subcortical white matter of the frontal, temporal and parietal lobes. The astrocytes were labeled by both tau antibodies, and simultaneously by GFAP. Their location appeared random, unrelated to variations in plaque and tangle load, myelin density, or gliosis. Conclusions: Similar argyrophilic astrocytes are present in frontotemporal lobar degeneration taupathies, notably in Pick’s disease, and in isolation in two reported cases of primary progressive aphasia. We hypothesize that the occurrence of severe language impairment at onset in AD is likely related to lesions distinct from plaques and neurofibrillary tangles O1-01-02 ALZHEIMER’S DISEASE WITH RELATIVE HIPPOCAMPAL SPARING: A DISTINCT CLINICOPATHOLOGIC VARIANT Melissa E. Murray, Dennis Dickson, Mayo Clinic College of Medicine, Jacksonville, FL, USA. Contact e-mail: murray.melissa@mayo.edu Background: Neuronal loss and neurofibrillary tangles (NFT) are characteristically severe in the medial temporal lobe, including the hippocampus (Hp), in Alzheimer’s disease (AD). Atrophy of the Hp on antemortem structural imaging correlates with conversion of at-risk individuals to AD and clinical progression of AD. On the other hand, at autopsy a subset of AD cases have relative preservation of the Hp with respect to atrophy and NFT density. Methods: The Mayo Clinic Jacksonville brain bank database was queried for AD cases with complete quantitative data and a Braak NFT stage of V or VI. 718 AD cases were identified, including 305 men and 413 women, ranging in age from 37 to 103 years. They were subdivided into two groups based upon the relative density of NFT in the Hp and convexity cortices. Maximal NFT density was assessed at high magnification with thioflavin-S fluorescent microscopy in four sectors of hippocampus (endplate, CA2/3, CA1, and subiculum) and three association cortices (superior temporal, midfrontal, and inferior parietal) and a primary cortex (visual cortex). A Braak NFT stage was assigned on each based upon the distribution of NFT. Results: The AD/HpSp group (N 42) were significantly different from AD with respect to NFT densities in all but the primary visual cortex. They had significantly fewer NFT (p 0.01) in the endplate, CA2/3, CA1 and subiculum. In contrast, the NFT density in superior temporal, mid-frontal and inferior parietal cortices were all significantly (p 0.001) higher in AD/HpSp compared to AD. The AD/HpSp group was significantly younger (average 70 vs. 80 years) and the male:female ratio was greater in AD/HpSp than in AD (0.6 vs. 0.4). The APOE e4 carrier frequency was also lower in AD/HpSp (33% vs. 62%). Conclusions: Our data suggests that AD/HpSp is an uncommon variant of AD accounting for about 6% of AD cases at autopsy. These cases have disproportionately more cortical than Hp neurofibrillary pathology. They also tend to be men, to have a younger age at death, and to be negative for APOE e4. Future studies are needed to determine if these individuals have distinctive clinical and imaging features. O1-01-03 THE MOST FREQUENT CAUSE OF DEMENTIA IN A BRAZILIAN SAMPLE: A NEUROPATHOLOGICAL STUDY Lea T. Grinberg, Renata E. L. Ferretti, Renata E. P. Leite, Eliza G. Moreira, Ana T. L. Alho, José M. Farfel, Silmara P. Pacheco, Carlos A. G. Pasqualucci, Kenji Ueda, Wilson Jacob, Ricardo Nitrini, Brazilian Aging Brain Study Group, University of Sao Paulo, Sao Paulo, Brazil; Tokyo Psychiatrics Institute, Tokyo, Japan. Contact e-mail: leagrinberg@usp.br Background: Alzheimer’s disease (AD) has been considered the most frequent cause of dementia in Brazil, but until now this hypothesis had not been confirmed by clinico-pathological studies. We objective to investigate the underlying neuropathological diagnoses in a sample of Brazilian cases of dementia sourced from a general autopsy service. Methods: A sample of 82 cases of dementia (53 women; mean age 78.5 10.6; years of schooling: 3.1 3.1, 74.4% Caucasian) of the Brain Bank of the Brazilian Aging Brain Study Group was randomly selected for the study. Diagnosis of dementia was established through a postmortem interview with an informant, usually a relative of the deceased. The interview includes a series of semi-structured scales and questionnaires that cover major functional abilities and are validated for assessT106 Oral O1-01: Diagnosis and Clinical Course: Molecular Pathology and Histopathology 1