Preclinical evidence of Alzheimer changes: convergent cerebrospinal fluid biomarker and fluorodeoxyglucose positron emission tomography findings.
BACKGROUND
Alterations in cerebrospinal fluid (CSF) tau and beta-amyloid peptide 1-42 (Abeta(42)) 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.


METHODS
Cohort study.


METHODS
Alzheimer disease research center.


METHODS
Twenty individuals without dementia aged 46 to 83 years.


METHODS
Lumbar CSF sampling and FDG-PET imaging of CMRglu. The CSF Abeta(42), tau, and tau phosphorylated at threonine 181 (ptau(181)) levels were measured using immunobead-based multiplex assays.


METHODS
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 ptau(181) levels and CMRglu in the posterior cingulate, precuneus, and parahippocampal regions. In contrast, a limited positive correlation was found between CSF Abeta(42) levels and CMRglu in the inferior temporal cortex. Volume-of-interest analyses confirmed negative associations between CSF tau and ptau(181) levels and CMRglu in the parietal and medial parietal lobes and a positive association between CSF Abeta(42) levels and CMRglu in the parahippocampal gyrus.


CONCLUSIONS
In healthy individuals, higher CSF tau and ptau(181) concentrations were associated with more severe hypometabolism in several brain regions affected very early in AD, whereas lower CSF Abeta(42) concentrations were associated with hypometabolism only in the medial temporal lobe. This suggests that early tau and Abeta 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.
Petrie
Eric C
EC
Mail Code S-182-GRECC, Veterans Affairs Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA. eric.petrie@med.va.gov
Cross
Donna J
DJ
Galasko
Douglas
D
Schellenberg
Gerard D
GD
Raskind
Murray A
MA
Peskind
Elaine R
ER
Minoshima
Satoshi
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000032:analysis / Q000134:cerebrospinal fluid; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose