- Email: [email protected]
Utility and impact of cerebrospinal fluid studies on dementia diagnosis in a specialty dementia practice
P376
Poster Presentations: P1
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.
be used in the clinical setting. It will be important to use lumbar puncture and biomarkers appropriately as the diagnosis and management of dementia evolves. As a first step in this process, we looked at current actual use of lumbar puncture and CSF biomarkers in a university-based specialty dementia practice. Methods: Review of billing records and medical records for patients seen in the Washington University Memory Diagnostic Center, a university based dementia specialty practice, between July 1, 2007 to December 31, 2012. Diagnoses before and after LP, rationale for performing LP, laboratory tests requested and results were determined based on review of the records. Results: Between July 2007 and December 2012, 2025 new patients were seen by 8 clinicians (7 neurologists and 1 geriatrician) at the Memory Diagnostic Center. 72 patients (3.5%) underwent diagnostic lumbar puncture as part of their diagnostic evaluation. An additional 7 patients underwent lumbar puncture as part of a research study. The frequency of use of diagnostic LP varied among providers (range 1-18 LPs done/provider). 14 patients undergoing LP were under age 55 (range 42-88). Patients undergoing LP had a similar range of diagnoses as patients who did not undergo LP. CSF biomarkers for Alzheimer disease were requested on 60 of the 72 LPs performed (83%). Other tests performed included CSF VDRL, gait testing before and after LP, IgG synthesis rate, 14-3-3 protein, paraneoplastic antibody testing, CSF angiotensin converting enzyme (ACE) level and cytology. Several patients had gait testing before and after LP to assess for normal pressure hydrocephalus. Conclusions: Lumbar puncture is used infrequently in the diagnostic evaluation of patients with dementia, even in a specialty dementia practice. Further studies on the appropriate use and clinical impact of CSF studies are needed and will be even more important as diagnosis and treatment of dementias evolves in the coming years.
P1-099
P1-098
UTILITY AND IMPACT OF CEREBROSPINAL FLUID STUDIES ON DEMENTIA DIAGNOSIS IN A SPECIALTY DEMENTIA PRACTICE
Max Fleisher1, Bharadwaj Jilakara1, Elizabeth Grant2,3, John C. Morris4,5, Barbara Joy Snider1, 1Washington University, St. Louis, MO, USA; 2 Knight Alzheimer Disease Research Center, St. Louis, MO, USA; 3 Washington University School of Medicine, St. Louis, MO, USA; 4 Washington University School of Medicine, St. Louis, MO, USA; 5Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA. Contact e-mail: [email protected] Background: Current recommendations support the use of lum-
bar puncture (LP) in the diagnosis of dementia in certain settings. Recent research and new diagnostic criteria support the use of specific biomarkers of Alzheimer’s disease but there are no established criteria for when these biomarkers should
WHITE MATTER LESIONS BUT NOT LACUNES ARE ASSOCIATED WITH THE CSF LEVELS OF Ab38 AND Ab40, AND TO A LESSER DEGREE WITH CSF Ab42
Danielle van Westen1, Danielle Lindqvist1, Sebastian Palmqvist2, Erik Stomrud2, Lennart Minthon2, Katarina N€agga2, Kaj Blennow3, Henrik Zetterberg3, Oskar Hansson2, 1Lund University, Lund, Sweden; 2 Lund University, Malm€o, Sweden; 3Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, M€olndal, Sweden. Contact e-mail: oskar. [email protected] Background: The objective was to investigate the relationship between cerebrovascular disease and amyloid deposition including multiple forms of b-amyloid (Ab). Methods: The study comprised 647 individuals from the prospective Swedish BioFINDER study, including 267 healthy elderly, 165 cases with subjective cognitive decline (SCD), 195 cases with mild cognitive impairment (MCI) and 20 cases with Alzheimer’s disease (AD). White matter hyperintensities (WMH) and lacunes were quantified using images from a 3 Tesla MRI scanner. Cerebrospinal fluid (CSF) levels of Ab38, Ab40 and Ab42 were determined using ELISA. [18F]flutametamol uptake was determines using PET in a subpopulation (n¼350). Results: The levels of CSF Ab42, but not Ab38 and Ab40, were strongly associated with [18F]flutametamol uptake and were reduced
Poster Presentations: P1
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.
be used in the clinical setting. It will be important to use lumbar puncture and biomarkers appropriately as the diagnosis and management of dementia evolves. As a first step in this process, we looked at current actual use of lumbar puncture and CSF biomarkers in a university-based specialty dementia practice. Methods: Review of billing records and medical records for patients seen in the Washington University Memory Diagnostic Center, a university based dementia specialty practice, between July 1, 2007 to December 31, 2012. Diagnoses before and after LP, rationale for performing LP, laboratory tests requested and results were determined based on review of the records. Results: Between July 2007 and December 2012, 2025 new patients were seen by 8 clinicians (7 neurologists and 1 geriatrician) at the Memory Diagnostic Center. 72 patients (3.5%) underwent diagnostic lumbar puncture as part of their diagnostic evaluation. An additional 7 patients underwent lumbar puncture as part of a research study. The frequency of use of diagnostic LP varied among providers (range 1-18 LPs done/provider). 14 patients undergoing LP were under age 55 (range 42-88). Patients undergoing LP had a similar range of diagnoses as patients who did not undergo LP. CSF biomarkers for Alzheimer disease were requested on 60 of the 72 LPs performed (83%). Other tests performed included CSF VDRL, gait testing before and after LP, IgG synthesis rate, 14-3-3 protein, paraneoplastic antibody testing, CSF angiotensin converting enzyme (ACE) level and cytology. Several patients had gait testing before and after LP to assess for normal pressure hydrocephalus. Conclusions: Lumbar puncture is used infrequently in the diagnostic evaluation of patients with dementia, even in a specialty dementia practice. Further studies on the appropriate use and clinical impact of CSF studies are needed and will be even more important as diagnosis and treatment of dementias evolves in the coming years.
P1-099
P1-098
UTILITY AND IMPACT OF CEREBROSPINAL FLUID STUDIES ON DEMENTIA DIAGNOSIS IN A SPECIALTY DEMENTIA PRACTICE
Max Fleisher1, Bharadwaj Jilakara1, Elizabeth Grant2,3, John C. Morris4,5, Barbara Joy Snider1, 1Washington University, St. Louis, MO, USA; 2 Knight Alzheimer Disease Research Center, St. Louis, MO, USA; 3 Washington University School of Medicine, St. Louis, MO, USA; 4 Washington University School of Medicine, St. Louis, MO, USA; 5Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA. Contact e-mail: [email protected] Background: Current recommendations support the use of lum-
bar puncture (LP) in the diagnosis of dementia in certain settings. Recent research and new diagnostic criteria support the use of specific biomarkers of Alzheimer’s disease but there are no established criteria for when these biomarkers should
WHITE MATTER LESIONS BUT NOT LACUNES ARE ASSOCIATED WITH THE CSF LEVELS OF Ab38 AND Ab40, AND TO A LESSER DEGREE WITH CSF Ab42
Danielle van Westen1, Danielle Lindqvist1, Sebastian Palmqvist2, Erik Stomrud2, Lennart Minthon2, Katarina N€agga2, Kaj Blennow3, Henrik Zetterberg3, Oskar Hansson2, 1Lund University, Lund, Sweden; 2 Lund University, Malm€o, Sweden; 3Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, M€olndal, Sweden. Contact e-mail: oskar. [email protected] Background: The objective was to investigate the relationship between cerebrovascular disease and amyloid deposition including multiple forms of b-amyloid (Ab). Methods: The study comprised 647 individuals from the prospective Swedish BioFINDER study, including 267 healthy elderly, 165 cases with subjective cognitive decline (SCD), 195 cases with mild cognitive impairment (MCI) and 20 cases with Alzheimer’s disease (AD). White matter hyperintensities (WMH) and lacunes were quantified using images from a 3 Tesla MRI scanner. Cerebrospinal fluid (CSF) levels of Ab38, Ab40 and Ab42 were determined using ELISA. [18F]flutametamol uptake was determines using PET in a subpopulation (n¼350). Results: The levels of CSF Ab42, but not Ab38 and Ab40, were strongly associated with [18F]flutametamol uptake and were reduced