overlapping profiles of aβ peptides in the alzheimers disease and pathological aging brains重叠的aβ肽在阿尔茨海默氏症和病理性老化的大脑.pdfVIP

Moore et al. Alzheimer ’s Research Therapy 2012, 4:18 /content/4/3/18 RESEARCH ARTICLE Open Access Overlapping profiles of Ab peptides in the Alzheimer’s disease and pathological aging brains 1 1 1 2 3 3 Brenda D Moore , Paramita Chakrabarty , Yona Levites , Tom L Kukar , Ann-Marie Baine , Tina Moroni , 1 3 3 1* Thomas B Ladd , Pritam Das , Dennis W Dickson and Todd E Golde Abstract Introduction: A hallmark of Alzheimer’s disease (AD) is the presence of senile plaques composed of aggregated amyloid b (Ab) peptides. Pathological aging (PA) is a postmortem classification that has been used to describe brains with plaque pathology similar in extent to AD, minimal cortical tau pathology, and no accompanying history of cognitive decline in the brain donor prior to death. PA may represent either a prodromal phase of AD, a benign form of Ab accumulation, or inherent individual resistance to the toxic effects of Ab accumulation. To attempt to distinguish between these possibilities we have systematically characterized Ab peptides in a postmortem series of PA, AD and non-demented control (NDC) brains. Methods: Ab 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 Ab sandwich ELISAs, 2) immunoprecipitation followed by mass spectrometry (IP/MS) and 3) western blotting. These studies enabled us to asses Ab levels and solubility, peptide profiles and oligomeric assemblies. Results: In almos