Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis

Publication date: January 2017 Source:The Lancet Neurology, Volume 16, Issue 1 Author(s): David J Irwin, Murray Grossman, Daniel Weintraub, Howard I Hurtig, John E Duda, Sharon X Xie, Edward B Lee, Vivianna M Van Deerlin, Oscar L Lopez, Julia K Kofler, Peter T Nelson, Gregory A Jicha, Randy Woltjer, Joseph F Quinn, Jeffery Kaye, James B Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C Dirk Keene, Thomas J Montine, Cyrus P Zabetian, John Q Trojanowski Background Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies. Methods In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of tau neurofibrillary tangles, neuritic plaques, α-synuclein inclusions, and other pathological changes in cortical regions. These samples were graded on an ordinal scale and genotyped for variants associated with synucleinopathies. We assessed the interval from onset of motor symptoms to onset o...
Source: The Lancet Neurology - Category: Neurology Source Type: research