University of California, San Diego

Grant Detail

The grant detail shows the name of the PI, active dates of the project, the funding institute and the abstract of the grant. This abstract is what is used to create the fingerprint of the grant. If any publications referencing this grant are found in the data, they will be listed here as well.

Biomarkers in Aging, MCI and Alzheimer's Disease

Galasko, Douglas

30 September 2003 - 31 July 2008
NATIONAL INSTITUTE ON AGING
Total Funding: $ 2,137,003

This proposal focuses on biological markers in cerebrospinal fluid (CSF) related to Alzheimer's Disease (AD). Biomarkers that are clearly related to the pathology of AD, namely A-beta42 (the major protein in plaques) and tau (found in tangles) can discriminate patients with AD from controls. Less is known about these and other biomarkers in mild cognitive impairment (MCI), which is often a prodromal stage of mild AD, and in relation to aging and to genetic and other risk factors for AD. In this proposal, 4 AD Research Centers will collaborate to obtain CSF and plasma samples from well-characterized subjects with AD, MCI and healthy controls spanning the age range 20-80. About 50% of subjects will contribute a set of serial CSF and plasma samples at 12 month follow-up. This project builds on an existing collaborative CSF and plasma bank, and aims to accrue and bank samples from over 500 subjects. A-beta processing, production, deposition and clearance are important factors in AD. These will be investigated by measuring levels of species of A-beta (A-beta 38, 40 and 42) and of secreted, cleaved forms of beta-amyloid precursor protein (APP), the parent molecule of A-beta, in CSF. Indices of neurodegeneration and tangle formation will be studied by quantifying CSF levels of tau and phospho-tau, and tau will be purified from CSF and sequenced. As indices of oxidative damage and inflammation, mechanisms implicated in neuronal damage in AD, biomarkers such as F-2 isoprostanes, S100B and alpha1ACT will be measured. The relationship between these biomarkers and age, sex, diagnosis (normal, MCI, mild AD), degree of cognitive impairment, and genetic risk factors for AD (apolipoprotein E [ApoE] and CYP46 genotypes) will be examined, and the extent of change in biomarkers over 12 months will be analyzed. Banked CSF and plasma will be available for further research into novel biomarkers, including broad-based proteomic studies.

8 Resulting Publications

• 1.

  2011

  Carlos Cruchaga; Petra Nowotny; John S K Kauwe; Perry G Ridge; Kevin Mayo; Sarah Bertelsen; Anthony Hinrichs; Anne M Fagan; David M Holtzman; John C Morris; et al.

  Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease.

  Archives of neurology 2011;68(8):1013-9.

• 2.

  2011

  Richard J Perrin; Rebecca Craig-Schapiro; James P Malone; Aarti R Shah; Petra Gilmore; Alan E Davis; Catherine M Roe; Elaine R Peskind; Ge Li; Douglas R Galasko; et al.

  Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease.

  PloS one 2011;6(1):e16032.

• 3.

  2011

  John S K Kauwe; Carlos Cruchaga; Celeste M Karch; Brooke Sadler; Mo Lee; Kevin Mayo; Wayne Latu; Manti Su'a; Anne M Fagan; David M Holtzman; et al.

  Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease.

  PloS one 2011;6(2):e15918.

• 4.

  2010

  Erik Portelius; Nenad Bogdanovic; Mikael K Gustavsson; Inga Volkmann; Gunnar Brinkmalm; Henrik Zetterberg; Bengt Winblad; Kaj Blennow

  Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer's disease.

  Acta neuropathologica 2010;120(2):185-93.

• 5.

  2009

  Eric C Petrie; Donna J Cross; Douglas Galasko; Gerard D Schellenberg; Murray A Raskind; Elaine R Peskind; Satoshi Minoshima

  Preclinical evidence of Alzheimer changes: convergent cerebrospinal fluid biomarker and fluorodeoxyglucose positron emission tomography findings.

  Archives of neurology 2009;66(5):632-7.

• 6.

  2009

  Ge Li; Elaine R Peskind; Steven P Millard; Peter Chi; Izabela Sokal; Chang-En Yu; Lynn M Bekris; Murray A Raskind; Douglas R Galasko; Thomas J Montine

  Cerebrospinal fluid concentration of brain-derived neurotrophic factor and cognitive function in non-demented subjects.

  PloS one 2009;4(5):e5424.

• 7.

  2006

  Elaine R Peskind; Ge Li; Jane Shofer; Joseph F Quinn; Jeffrey A Kaye; Chris M Clark; Martin R Farlow; Charles DeCarli; Murray A Raskind; Gerard D Schellenberg; et al.

  Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition.

  Archives of neurology 2006;63(7):936-9.

• 8.

  2005

  Elaine R Peskind; Robert Riekse; Joseph F Quinn; Jeffrey Kaye; Christopher M Clark; Martin R Farlow; Charles Decarli; Charles Chabal; Darcy Vavrek; Murray A Raskind; et al.

  Safety and acceptability of the research lumbar puncture.

  Alzheimer disease and associated disorders 2005;19(4):220-5.

Scientific Context

This section shows information that has been computed by using the fingerprint of the grant, including related publications, related experts and related grants - all with fingerprints representing significant amounts of overlap between their fingerprint and this grant. The red dots indicate whether those experts or terms actually appear within this grant, showing potential and actual connections.