Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease

• Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

AD

Alzheimer's disease

Biomarkers

Cerebrospinal fluid

Parallel reaction monitoring (PRM)

Suspension bead array (SBA)

alpha 1 aantitrypsin

alpha 1 antichymotrypsin

apolipoprotein

biological marker

cathepsin D

cholecystokinin

creatine kinase B type

dickkopf related protein 3

fibrinogen alpha

fructose bisphosphate aldolase C

glucose regulated protein 94

inter alpha trypsin inhibitor heavy chain H1

leucine rich alpha 2 glycoprotein

neurobeachin

neurofilament medium polypeptide

neuromodulin

plasminogen

prosaposin

protein S100B

SPARC like protein 1

unclassified drug

vascular cell adhesion protein 1

adult

aged

Alzheimer disease

Article

clinical article

cohort analysis

controlled study

correlational study

disease course

female

human

male

mass spectrometry

middle aged

mild cognitive impairment

multiple reaction monitoring

priority journal

protein blood level

protein cerebrospinal fluid level

protein microarray

suspension bead array

very elderly

AD

Alzheimer's disease

Biomarkers

Cerebrospinal fluid

Parallel reaction monitoring (PRM)

Suspension bead array (SBA)

alpha 1 aantitrypsin

alpha 1 antichymotrypsin

apolipoprotein

biological marker

cathepsin D

cholecystokinin

creatine kinase B type

dickkopf related protein 3

fibrinogen alpha

fructose bisphosphate aldolase C

glucose regulated protein 94

inter alpha trypsin inhibitor heavy chain H1

leucine rich alpha 2 glycoprotein

neurobeachin

neurofilament medium polypeptide

neuromodulin

plasminogen

prosaposin

protein S100B

SPARC like protein 1

unclassified drug

vascular cell adhesion protein 1

adult

aged

Alzheimer disease

Article

clinical article

cohort analysis

controlled study

correlational study

disease course

female

human

male

mass spectrometry

middle aged

mild cognitive impairment

multiple reaction monitoring

priority journal

protein blood level

protein cerebrospinal fluid level

protein microarray

suspension bead array

very elderly

Publication and Content Type

ref (subject category)

art (subject category)