Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.

Abstract

Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 ± 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE > 20 points, n=30) and moderate (MMSE < 21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [κ]=0.34, p=0.016) for t-tau, 68% (κ=0.10, n.s.) for p-tau181, and 68% (κ=0.04, n.s.) for Aβ1-42. No significant agreement was found in the mild AD subgroup, while there was a strong agreement for t-tau (94%, κ=0.77, p=0.001) and p-tau181 (88%, κ=0.60, p=0.014) in the moderate AD group. A significant agreement between the FDG-PET and CSF tau findings in patients with AD supports the view that both are markers of neurodegeneration. CSF tau proteins and FDG-PET might substitute each other as supportive diagnostic tools in patients with suspected moderate-to-severe Alzheimer's dementia, while this is not the case in subjects at an earlier disease stage.

• Authors: Igor Yakushev, Matthias J Muller, Hans-Georg Buchholz, Ulrike Lang, Heidi Rossmann, Harald Hampel, Mathias Schreckenberger, Andreas Fellgiebel
• Journal: Current Alzheimer research (Curr Alzheimer Res) Vol. 9 Issue 2 Pg. 241-7 (Feb 2012) ISSN: 1875-5828 [Electronic] United Arab Emirates
• PMID: 22044023 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• Apolipoprotein E4
• Biomarkers
• Cerebrospinal Fluid Proteins
• Peptide Fragments
• amyloid beta-protein (1-42)
• tau Proteins
• Fluorodeoxyglucose F18

Topics

• Aged
• Alzheimer Disease (cerebrospinal fluid, complications, diagnostic imaging)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Apolipoprotein E4 (genetics)
• Area Under Curve
• Biomarkers
• Cerebrospinal Fluid Proteins (cerebrospinal fluid)
• Cognition Disorders (cerebrospinal fluid, diagnostic imaging, etiology)
• Female
• Fluorodeoxyglucose F18
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Neuropsychological Tests
• Peptide Fragments (cerebrospinal fluid)
• Positron-Emission Tomography
• Psychiatric Status Rating Scales
• Retrospective Studies
• Sensitivity and Specificity
• tau Proteins (cerebrospinal fluid)