scholarly journals Synaptic Molecular and Neurophysiological Markers Are Independent Predictors of Progression in Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Una Smailovic ◽  
Ingemar Kåreholt ◽  
Thomas Koenig ◽  
Nicholas J. Ashton ◽  
Bengt Winblad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Global Field ◽  
Prognostic Indicators ◽  
Early Event ◽  
Functional Markers ◽  
Beta Band ◽  
Global Field Power ◽  
Synaptic Markers ◽  
Eeg Recordings

Background: Cerebrospinal fluid (CSF) neurogranin and quantitative electroencephalography (qEEG) are potential molecular and functional markers of synaptic pathology in Alzheimer’s disease (AD). Synaptic markers have emerged as candidate prognostic indicators of AD since synaptic degeneration was shown to be an early event and the best correlate of cognitive deficits in patients along the disease continuum. Objective: The present study investigated the association between CSF neurogranin and qEEG measures as well as their potential to predict clinical deterioration in mild cognitive impairment (MCI) patients. Methods: Patients diagnosed with MCI (n = 99) underwent CSF conventional AD biomarkers and neurogranin analysis and resting-state EEG recordings. The study population was further stratified into stable (n = 41) and progressive MCI (n = 31), based on the progression to AD dementia during two years follow-up. qEEG analysis included computation of global field power and global field synchronization in four conventional frequency bands. Results: CSF neurogranin levels were associated with theta power and synchronization in the progressive MCI group. CSF neurogranin and qEEG measures were significant predictors of progression to AD dementia, independent of baseline amyloid status in MCI patients. A combination of CSF neurogranin with global EEG power in theta and global EEG synchronization in beta band exhibited the highest classification accuracy as compared to either of these markers alone. Conclusion: qEEG and CSF neurogranin are independent predictors of progression to AD dementia in MCI patients. Molecular and neurophysiological synaptic markers may have additive value in a multimodal diagnostic and prognostic approach to dementia.

scholarly journals Decreased Global EEG Synchronization in Amyloid Positive Mild Cognitive Impairment and Alzheimer’s Disease Patients—Relationship to APOE ε4

2021 ◽  
Vol 11 (10) ◽  
pp. 1359
Author(s):  
Una Smailovic ◽  
Charlotte Johansson ◽  
Thomas Koenig ◽  
Ingemar Kåreholt ◽  
Caroline Graff ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Quantitative Eeg ◽  
Global Field ◽  
Compensatory Mechanism ◽  
Global Field Power ◽  
Apoe Ε4 ◽  
Ε4 Allele

The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimer’s disease (AD) that has been linked to changes in brain structure and function as well as to different biological subtypes of the disease. The present study aimed to investigate the association of APOE ε4 genotypes with brain functional impairment, as assessed by quantitative EEG (qEEG) in patients on the AD continuum. The study population included 101 amyloid positive patients diagnosed with mild cognitive impairment (MCI) (n = 50) and AD (n = 51) that underwent resting-state EEG recording and CSF Aβ42 analysis. In total, 31 patients were APOE ε4 non-carriers, 42 were carriers of one, and 28 were carriers of two APOE ε4 alleles. Quantitative EEG analysis included computation of the global field power (GFP) and global field synchronization (GFS) in conventional frequency bands. Amyloid positive patients who were carriers of APOE ε4 allele(s) had significantly higher GFP beta and significantly lower GFS in theta and beta bands compared to APOE ε4 non-carriers. Increased global EEG power in beta band in APOE ε4 carriers may represent a brain functional compensatory mechanism that offsets global EEG slowing in AD patients. Our findings suggest that decreased EEG measures of global synchronization in theta and beta bands reflect brain functional deficits related to the APOE ε4 genotype in patients that are on a biomarker-verified AD continuum.

Global field power and low resolution electromagnetic tomography solutions in Alzheimer's disease

2002 ◽  
Vol 1232 ◽  
pp. 751-755
Author(s):  
Masafumi Yoshimura ◽  
Hailing Zhang ◽  
Toshiaki Isotani ◽  
Chiharu Tamagaki ◽  
Tsunetaka Yoshida ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Global Field ◽  
Low Resolution ◽  
Global Field Power ◽  
Electromagnetic Tomography

Assembly of Aβ Amyloid Protofibrils:  An in Vitro Model for a Possible Early Event in Alzheimer's Disease†

Biochemistry ◽  
1999 ◽  
Vol 38 (28) ◽  
pp. 8972-8980 ◽  
Author(s):  
James D. Harper ◽  
Stanislaus S. Wong ◽  
Charles M. Lieber ◽  
Peter T. Lansbury
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vitro Model ◽  
Early Event ◽  
Aβ Amyloid ◽  
Vitro Model

scholarly journals RTP801/REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer’s disease

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Leticia Pérez-Sisqués ◽  
Anna Sancho-Balsells ◽  
Júlia Solana-Balaguer ◽  
Genís Campoy-Campos ◽  
Marcel Vives-Isern ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Mrna Levels ◽  
Spine Density ◽  
Memory Impairments ◽  
Protein Levels ◽  
Synaptic Markers ◽  
5Xfad Mice

AbstractRTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death. Its downregulation in Parkinson’s and Huntington’s disease models ameliorates the pathological phenotypes. In the context of Alzheimer’s disease (AD), the coding gene for RTP801, DDIT4, is responsive to Aβ and modulates its cytotoxicity in vitro. Also, RTP801 mRNA levels are increased in AD patients’ lymphocytes. However, the involvement of RTP801 in the pathophysiology of AD has not been yet tested. Here, we demonstrate that RTP801 levels are increased in postmortem hippocampal samples from AD patients. Interestingly, RTP801 protein levels correlated with both Braak and Thal stages of the disease and with GFAP expression. RTP801 levels are also upregulated in hippocampal synaptosomal fractions obtained from murine 5xFAD and rTg4510 mice models of the disease. A local RTP801 knockdown in the 5xFAD hippocampal neurons with shRNA-containing AAV particles ameliorates cognitive deficits in 7-month-old animals. Upon RTP801 silencing in the 5xFAD mice, no major changes were detected in hippocampal synaptic markers or spine density. Importantly, we found an unanticipated recovery of several gliosis hallmarks and inflammasome key proteins upon neuronal RTP801 downregulation in the 5xFAD mice. Altogether our results suggest that RTP801 could be a potential future target for theranostic studies since it could be a biomarker of neuroinflammation and neurotoxicity severity of the disease and, at the same time, a promising therapeutic target in the treatment of AD.

Therapy for Alzheimer’s disease: Missing Targets and Functional Markers?

2021 ◽  
pp. 101318
Author(s):  
Milan Stoiljkovic ◽  
Tamas L. Horvath ◽  
Mihály Hajós
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Markers
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