Cortical phosphorylated α-Synuclein levels correlate with brain wave spectra in Parkinson's disease

Abstract

Objectives Quantitative EEG features have been identified as surrogates and predictors of cognitive decline/dementia, a common feature of progressive Parkinson's disease. The biochemical correlates for altered quantitative EEG features are unknown. Our primary objective was to test the hypothesis that quantitative EEG measures correlate with cortical levels of phosphorylated α-synuclein, a modified form of the synaptic protein α-synuclein, in Parkinson's disease cases, in contrast to other pathology-associated proteins. A secondary objective was to explore the same correlations among cellular fractions of these proteins. Methods We used posterior cingulate cortex autopsy tissue from 44 Parkinson's disease subjects with various degrees of cognitive decline, who had undergone EEG. In this brain region, which is a major hub of the default mode network, biochemical measurements for levels of phosphorylated α-synuclein, unmodified α-synuclein, Aβ peptide, phosphorylated tau and key synaptic proteins were analyzed, and data correlated with spectral EEG measures. Results Findings revealed significant correlations between background rhythm peak frequency and all bandpower values (highest in delta bandpower) with total phosphorylated α-synuclein, but not any correlation with total α-synuclein, phosphorylated tau protein, Aβ peptide or synaptic proteins. Certain fractions of synaptosomal-associated protein 25 showed correlation with some quantitative EEG measures. Conclusions These data show association between increased phosphorylation of α-synuclein and the abnormal EEG signatures of cognitive decline. Results suggest quantitative EEG may provide an in vivo approximation of phosphorylated α-synuclein in Parkinson's disease cortex. This adds to previous evidence that quantitative EEG measures can be considered valid biomarkers of Parkinson's disease cognitive decline.

Prediction of cognitive worsening in de novo Parkinson's disease: Clinical use of biomarkers

“…Moreover, we provide cutoff values that may be used in clinical practice for both wake EEG and 123 I‐FP‐CIT‐SPECT. Reduced background EEG frequencies have been recently found to be related to cortical levels of phosphorylated α‐synuclein in posterior cingulate cortex autopsy tissue . The authors suggested that the qEEG measure can be a valuable surrogate biomarker of PD cognitive decline …”

Mitochondrial dysfunction in Parkinson's disease

“…Therefore, quantitative EEG measures in vivo can be considered as valid biomarker of cognitive decline in PD (Caviness et al . ). Currently there are no cerebrospinal biomarkers.…”

Abnormalities of Cortical Neural Synchronization Mechanisms in Subjects with Mild Cognitive Impairment due to Alzheimer’s and Parkinson’s Diseases: An EEG Study

“…The procedure is reported in the following. Firstly, we selected the standard fixed frequency bands in line with previous field studies of our research group [14,[32][33][34][35], namely delta (2-4 Hz), theta (4-8 Hz), alpha1 (8.5-10 Hz), alpha2 (10.5-13 Hz), beta1 (13.5-20 Hz), beta2 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and gamma (30-40 Hz). Secondly, eLORETA solutions using the following fixed frequency bands were computed.…”

“…An early investigation reported similar abnormalities of posterior delta power in ADD and PDD subjects [26], while the delta and the theta power averaged in the whole scalp ("global") were greater in PDD patients than in ADD, PD, and Nold individuals [27]. It was posited that these effects were related to phosphorylation of ␣-synuclein in the posterior cingulate cortex (hub of the default mode network), namely the higher the ␣-synuclein load, the higher the global delta, the lower the global alpha power, and the lower the frequency alpha peak [28]. Furthermore, previous rsEEG studies showed that the global delta power did fluctuate over a few minutes more in PDD than ADD patients [19,[29][30][31].…”