%0 Journal Article
%T Overlapping profiles of A¦Â peptides in the Alzheimer's disease and pathological aging brains
%A Brenda D Moore
%A Paramita Chakrabarty
%A Yona Levites
%A Tom L Kukar
%A Ann-Marie Baine
%A Tina Moroni
%A Thomas B Ladd
%A Pritam Das
%A Dennis W Dickson
%A Todd E Golde
%J Alzheimer's Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/alzrt121
%X A¦Â was sequentially extracted with tris buffered saline (TBS), radioimmunoprecipitation buffer (RIPA), 2% sodium dodecyl sulfate (SDS) and 70% formic acid (FA) from the pre-frontal cortex of 16 AD, eight PA, and six NDC patients. These extracts were analyzed by 1) a panel of A¦Â sandwich ELISAs, 2) immunoprecipitation followed by mass spectrometry (IP/MS) and 3) western blotting. These studies enabled us to asses A¦Â levels and solubility, peptide profiles and oligomeric assemblies.In almost all extracts (TBS, RIPA, 2% SDS and 70% FA) the average levels of A¦Â1-40, A¦Â1-42, A¦Â total, and A¦Âx-42 were greatest in AD. On average, levels were slightly lower in PA, and there was extensive overlap between A¦Â levels in individual PA and AD cases. The profiles of A¦Â peptides detected using IP/MS techniques also showed extensive similarity between the PA and AD brain extracts. In select AD brain extracts, we detected more amino-terminally truncated A¦Â peptides compared to PA patients, but these peptides represented a minor portion of the A¦Â observed. No consistent differences in the A¦Â assemblies were observed by western blotting in the PA and AD groups.We found extensive overlap with only subtle quantitative differences between A¦Â levels, peptide profiles, solubility, and SDS-stable oligomeric assemblies in the PA and AD brains. These cross-sectional data indicate that A¦Â accumulation in PA and AD is remarkably similar. Such data would be consistent with PA representing a prodromal stage of AD or a resistance to the toxic effects of A¦Â.Alzheimer's disease (AD) is characterized by large numbers of extracellular amyloid plaques with dense amyloid cores that are associated with dystrophic neurites and neuroinflammatory changes as well as intraneuronal neurofibrillary tangles. Pathological aging (PA) patients also have abundant and widespread amyloid plaques; however, these plaques have typically been described as diffuse in nature. In PA there are fewer cored plaques and there is
%U http://alzres.com/content/4/3/18