This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Alzheimer Disease  • Nutritional and Metabolic Disorders  • Metabolic Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

Convergent Cerebrospinal Fluid Biomarker and Fluorodeoxyglucose Positron Emission Tomography Findings

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

Arch Neurol. 2009;66(5):632-637.

Background  Alterations in cerebrospinal fluid (CSF) tau and β-amyloid peptide 1-42 (Aβ₄₂) levels and rates of cerebral glucose metabolism (CMRglu) on fluorodeoxyglucose positron emission tomography (FDG-PET) occur years before clinical symptoms of Alzheimer disease (AD) become manifest, but their relationship remains unclear.

Objective  To determine whether CSF AD biomarker levels and CMRglu in healthy individuals correlate in brain structures affected early in AD.

Design  Cohort study.

Setting  Alzheimer disease research center.

Participants  Twenty individuals without dementia aged 46 to 83 years.

Interventions  Lumbar CSF sampling and FDG-PET imaging of CMRglu. The CSF Aβ₄₂, tau, and tau phosphorylated at threonine 181 (ptau₁₈₁) levels were measured using immunobead-based multiplex assays.

Main Outcome Measures  Correlations between CMRglu and CSF biomarker levels were analyzed via voxel-based and volume-of-interest approaches.

Results  Voxel-based analyses demonstrated significant negative correlations between CSF tau and ptau₁₈₁ levels and CMRglu in the posterior cingulate, precuneus, and parahippocampal regions. In contrast, a limited positive correlation was found between CSF Aβ₄₂ levels and CMRglu in the inferior temporal cortex. Volume-of-interest analyses confirmed negative associations between CSF tau and ptau₁₈₁ levels and CMRglu in the parietal and medial parietal lobes and a positive association between CSF Aβ₄₂ levels and CMRglu in the parahippocampal gyrus.

Conclusions  In healthy individuals, higher CSF tau and ptau₁₈₁ concentrations were associated with more severe hypometabolism in several brain regions affected very early in AD, whereas lower CSF Aβ₄₂ concentrations were associated with hypometabolism only in the medial temporal lobe. This suggests that early tau and Aβ abnormalities may be associated with subtle synaptic changes in brain regions vulnerable to AD. A longitudinal assessment of CSF and FDG-PET biomarkers is needed to determine whether these changes predict cognitive impairment and incipient AD.

Author Affiliations: Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System (Drs Petrie, Raskind, and Peskind) and Departments of Psychiatry and Behavioral Sciences (Drs Petrie, Raskind, and Peskind) and Radiology (Drs Cross and Minoshima), University of Washington, Seattle; Veterans Affairs Medical Center (Dr Galasko) and Department of Neurosciences (Dr Galasko), University of California, San Diego; and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia (Dr Schellenberg).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

This Month in Archives of Neurology
Arch Neurol. 2009;66(5):552-553.
FULL TEXT