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P1‐098: Utility and impact of cerebrospinal fluid studies on dementia diagnosis in a specialty dementia practice
Author(s) -
Fleisher Max,
Jilakara Bharadwaj,
Grant Elizabeth,
Morris John C.,
Snider Barbara Joy
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.295
Subject(s) - medicine , dementia , lumbar puncture , specialty , medical diagnosis , medical record , lumbar , disease , diagnostic accuracy , clinical practice , intensive care medicine , cerebrospinal fluid , pediatrics , physical therapy , surgery , pathology
with dementia and therefore represents an early diagnostic and therapeutic target for the treatment of Alzheimer’s disease (AD). In order to elucidate the mechanisms of peptide misfolding in the early stages of AD pathogenesis, it is important to develop sensitive and specific assays to identify and monitor key molecular triggers and biological markers before the development of clinical symptoms. Methods: High resolution mass spectrometry (LC-MS) and quantitative single reaction monitoring (SRM) mass spectrometry was used for the screening abeta peptide aggregation in vitro and ex vivo. Results: We have identified key molecular changes associated with Abeta peptide oligomerization using mass spectrometry. This discovery has enabled us to design novel epitope targets for antiabeta antibodies, which specifically target abeta at the early stages of peptide oligomerization but do not recognize the soluble, monomeric form of the peptide. Screening of human post-mortem brain tissue and CSF samples from AD patients and non-demented control subjects revealed that, these molecular changes of abeta peptide are a highly relevant feature observed in AD patients. Conclusions: Our findings show that the use of novel anti-abeta target epitope antibodies offers a new analytical tool for the identification of early molecular seeds of Abeta oligomers. These findings are crucial not only for understanding and targeting Abeta peptide aggregation, but also for monitoring the disease associated changes in levels of Abeta found in human biofluids.