Synaptic dysfunction is the best anatomical correlate of early cognitive impairment in Alzheimer's disease (AD). Electroencephalography (EEG) directly reflects brain electrical activity at the level of synapses. The aim of the present study was to investigate correlations of quantitative EEG measures, global field power (GFP) and global field synchronization (GFS), with conventional cerebrospinal fluid (CSF) biomarkers of neurodegeneration in patients diagnosed with subjective cognitive decline (n = 210), mild cognitive impairment (n = 230), and AD (n = 197). Decreased CSF amyloid β42 significantly correlated with increased theta and delta GFP, whereas increased p- and t-tau with decreased alpha and beta GFP. Decreased CSF amyloid β42 and increased p- and t-tau were significantly associated with decreased GFS alpha and beta. Subanalysis of the separate diagnostic groups demonstrated significant correlations between CSF biomarkers and generalized power and synchronization already in the subjective cognitive decline and mild cognitive impairment group. These results provide evidence that quantitative EEG measures are associated and possibly sensitive to distinct AD-like CSF biomarker profiles in cognitively impaired patients and are therefore promising early noninvasive markers of AD.
Currently established and employed biomarkers of Alzheimer's disease (AD) predominantly mirror AD-associated molecular and structural brain changes. While they are necessary for identifying disease-specific neuropathology, they lack a clear and robust relationship with the clinical presentation of dementia; they can be altered in healthy individuals, while they often inadequately mirror the degree of cognitive and functional deficits in affected subjects. There is growing evidence that synaptic loss and dysfunction are early events during the trajectory of AD pathogenesis that best correlate with the clinical symptoms, suggesting measures of brain functional deficits as candidate early markers of AD. Resting-state electroencephalography (EEG) is a widely available and noninvasive diagnostic method that provides direct insight into brain synaptic activity in real time. Quantitative EEG (qEEG) analysis additionally provides information on physiologically meaningful frequency components, dynamic alterations and topography of EEG signal generators, i.e. neuronal signaling. Numerous studies have shown that qEEG measures can detect disruptions in activity, topographical distribution and synchronization of neuronal (synaptic) activity such as generalized EEG slowing, reduced global synchronization and anteriorization of neuronal generators of fast-frequency resting-state EEG activity in patients along the AD continuum. Moreover, qEEG measures appear to correlate well with surrogate markers of AD neuropathology and discriminate between different types of dementia, making them promising low-cost and noninvasive markers of AD. Future large-scale longitudinal clinical studies are needed to elucidate the diagnostic and prognostic potential of qEEG measures as early functional markers of AD on an individual subject level.
HighlightsEEG microstate topographies differ between controls and memory clinic patients.Microstate parameters differ in a gradient-like manner in SCD, MCI and AD patients.Changes in topography of microstate class C correlate with CSF Aβ42 levels.Changes in topography of microstate class B correlate with CSF p-tau levels.EEG microstates detect early disruption of neurocognitive networks in AD.
Accumulated evidence suggests that the insulin-resistant brain state and cerebral glucose hypometabolism might be the cause, rather than the consequence, of the neurodegeneration found in a sporadic Alzheimer's disease (sAD). We have explored whether the insulin receptor (IR) and the glucose transporter-2 (GLUT2), used here as their markers, are the early targets of intracerebroventricularly (icv) administered streptozotocin (STZ) in an STZ-icv rat model of sAD, and whether their changes are associated with the STZ-induced neuroinflammation. The expression of IR, GLUT2 and glial fibrillary acidic protein (GFAP) was measured by immunofluorescence and western blot analysis in the parietal (PC) and the temporal (TC) cortex, in the hippocampus (HPC) and the hypothalamus. One hour after the STZ-icv administration (1.5 mg/kg), the GFAP immunoreactivity was significantly increased in all four regions, thus indicating the wide spread neuroinflammation, pronounced in the PC and the HPC. Changes in the GLUT2 (increment) and the IR (decrement) expression were mild in the areas close to the site of the STZ injection/release but pronounced in the ependymal lining cells of the third ventricle, thus indicating the possible metabolic implications. These results, together with the finding of the GLUT2-IR co-expression, and also the neuronal IR expression in PC, TC and HPC, indicate that the cerebral GLUT2 and IR should be further explored as the possible sAD etiopathogenic factors. It should be further clarified whether their alterations are the effect of a direct STZ-icv toxicity or they are triggered in a response to STZ-icv induced neuroinflammation.
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