–ѕа°±б>ю€ ')ю€€€&€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€м•Ѕ7 рњjbjbjUU .7|7|j €€€€€€l®®®®®®®Љмммм ш Љ®ґллл$^ ~H5-®ллллл5I®®џbIIIлц®®IлI∆I®® –яћ,∆Љ0мб:x0®∆ .∆ IЉЉ®®®®ўExtending the neuropathological spectrum of frontotemporal lobar degenerations: a review of 833 prospectively assessed dementia cases Author Block Lea Tenenholz Grinberg1,2, Rajka M. Liscic3,2, Tu Pang-hsien2, Daniel McKeel2, Deborah Carter2, Lisa Marie Taylor-Reinwald2, John C. Morris2, Nigel J. Cairns2, 1University of Sao Paulo, Sao Paulo, Brazil; 2Washington University in St Louis, St Louis, MO, USA; 3Institute for Medical Research and Occupational Health, Zagreb, Croatia. Contact e-mail: leagrinberg@usp.br Background: Frontotemporal lobar degenerations (FTLDs) are clinically and neuropathologically heterogeneous and may account for 5-10% of dementias. Advances in immunohistochemistry, biochemistry, and genetics have helped to define and continue to broaden the spectrum of neurodegenerative diseases that are FTLDs. Objectives: To determine the pathological spectrum and frequency of FTLDs in a cohort of individuals assessed at the Washington University AlzheimerТs Disease Research Center (WUADRC). Methods: Review of 833 prospectively assessed dementia cases (Clinical Dementia Rating e" 0.5) between 1988 and 2005 at the WUADRC and selection of cases with a neuropathological diagnosis of FTLD according to established and other neuropathological criteria. Brain tissue was processed and blocks taken according to the protocols of the WUADRC Neuropathology Core. Immunohistochemistry was performed on selected areas using antibodies against the following peptides or proteins: ≤-amyloid, phosphorylated tau, ±-synuclein, ubiquitin, ±-internexin, and valosin-containing protein. Results: Of the 833 dementia cases, 45 (5.4%) had a neuropathological diagnosis of FTLD or 6 had another neurodegenerative disease with clinical FTLD. There were 20 females (39.2%) and 31 males (60.1%). Nineteen of 51 cases (37.3%) had abnormal aggregates of tau in neurons and glia: PickТs Disease (n=2); corticobasal degeneration (n=11), argyrophilic grain disease (AGD, n=1), frontotemporal dementia with parkinsonism linked to chromosome 17 (n=2), tangle-only dementia (TOD, n=2), and one case of familial tauopathy with no tau mutation (n=1). However, the majority of the FTLD cases were characterized by tau-negative inclusions: FTLD with ubiquitin inclusions (FTLD-U, n=27, 53%), inclusion body myositis with Paget disease and frontotemporal dementia (IBMPFD, n=1), and hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS, n=2). Two cases of FTLD had no tau- or ubiquitin-positive inclusions. Co-existing hippocampal sclerosis was observed in 12 cases and AlzheimerТs disease type changes in 11 cases. Conclusion: Although FTLD-U is the most frequent FTLD in this prospectively assessed series, less common entities not typically included such as IBMPFD, AGD, TOD, and HDLS, may also have the clinical phenotype of FTLD and should be considered as part of the neuropathological spectrum of FTLDs. 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