Abstract
Higher neuronal or metabolic activity may contribute to Alzheimer's disease (AD) neuropathology. Systemic inflammation also increases the risk for developing AD, but it is unclear whether an effect on brain activity may play a role. Prior studies relating inflammation to regional brain glucose metabolism (fluorodeoxyglucose positron emission tomography; FDG-PET) had mixed results. In non-demented older adults, we related serum levels of tumor necrosis factor α (TNFα), an inflammatory marker, to FDG-PET signal in AD-relevant regions. We hypothesized that higher blood TNFα would be associated with higher FDG-PET signal. In 230 non-demented older adults (202 Mild Cognitive Impairment: MCI; 28 controls) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we used multiple linear regression to relate serum TNFα to FDG-PET signal in left temporal cortex and bilateral posterior cingulate – two regions that most consistently demonstrate MCI-related change. In a subset of 127 subjects who also had cerebrospinal fluid (CSF) Aβ42 and ptau181 assays, we related these measures to TNFα and to FDG-PET signal in the left temporal lobe. We controlled for age, sex, and diagnosis in all analyses. Higher TNFα was significantly associated with higher FDG-PET signal in the left temporal (omnibus p = 0.001; partial t for TNFα= 2.42; partial p for TNFα = 0.016) and mean bilateral temporal (omnibus p = 0.001; partial t for TNFα= 2.23; partial p for TNFα = 0.027) cortex, but not in bilateral cingulate (partial p for TNFα = 0.505). Higher CSF Aβ42 (omnibus p = 0.002; partial t for Aβ42= 2.78; partial p for Aβ42 = 0.006) and lower CSF ptau181 (trend: omnibus p = 0.011; partial t for ptau181= 1.83; partial p for ptau181= 0.070) were associated with greater FDG-PET signal in the left temporal lobe, but were not significantly associated with TNFα. Higher serum TNFα was associated with higher FDG-PET signal in the temporal lobe, but not with CSF levels of Aβ42 or ptau181, suggesting that this effect is unlikely to reflect inflammation resulting from this pathology. Because higher activity may lead to plaques and tangles, our findings suggest a way by which inflammation may increase AD risk.
Published Version
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