%0 Journal Article %J J Alzheimers Dis %D 2021 %T Synaptic Molecular and Neurophysiological Markers Are Independent Predictors of Progression in Alzheimer's Disease. %A Smailovic, Una %A Kåreholt, Ingemar %A Koenig, Thomas %A Ashton, Nicholas J %A Winblad, Bengt %A Höglund, Kina %A Nilsson, Per %A Zetterberg, Henrik %A Blennow, Kaj %A Jelic, Vesna %X

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.

%B J Alzheimers Dis %V 83 %P 355-366 %8 2021 Aug 31 %G eng %N 1 %R 10.3233/JAD-201234 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Association of Platelet Serotonin Levels in Alzheimer's Disease with Clinical and Cerebrospinal Fluid Markers. %A Tajeddinn, Walid %A Fereshtehnejad, Seyed-Mohammad %A Seed Ahmed, Mohammed %A Yoshitake, Takashi %A Kehr, Jan %A Shahnaz, Tasmin %A Milovanovic, Micha %A Behbahani, Homira %A Höglund, Kina %A Winblad, Bengt %A Cedazo-Minguez, Angel %A Jelic, Vesna %A Järemo, Petter %A Aarsland, Dag %X

INTRODUCTION: Serotonin (5-HT) is involved in the pathology of Alzheimer's disease (AD).

OBJECTIVE: We aimed to measure 5-HT level in platelets in AD and explore its association with cerebrospinal fluid (CSF), AD biomarkers (amyloid-β 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau)), and clinical symptoms.

METHODS: 15 patients with AD and 20 patients with subjective cognitive impairment (SCI) were included. 5-HT metabolites were measured, in a specific fraction, using high performance liquid chromatography with electrochemical detection (HPLC-ECD).

RESULTS: Significantly lower 5-HT concentrations were observed in AD patients compared to SCI patients both after normalization against total protein (p = 0.008) or platelet count (p = 0.019). SCI patients with lower 5-HT level have higher AD CSF biomarkers, total tau (p = 0.026) and tau/Aβ42 ratio (p = 0.001), compared to those with high 5-HT levels.

CONCLUSION: AD patients have reduced platelet 5-HT levels. In SCI, lower 5-HT content was associated with a higher AD-CSF biomarker burden.

%B J Alzheimers Dis %V 53 %P 621-30 %8 2016 May 04 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27163811?dopt=Abstract %R 10.3233/JAD-160022 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Pharmacological Modulations of the Serotonergic System in a Cell-Model of Familial Alzheimer's Disease. %A Tajeddinn, Walid %A Persson, Torbjörn %A Calvo-Garrido, Javier %A Seed Ahmed, Mohammed %A Maioli, Silvia %A Vijayaraghavan, Swetha %A Kazokoglu, Mehmet Selim %A Parrado-Fernández, Cristina %A Yoshitake, Takashi %A Kehr, Jan %A Francis, Paul %A Winblad, Bengt %A Höglund, Kina %A Cedazo-Minguez, Angel %A Aarsland, Dag %X

Serotonin (5-HT) plays a central role in the integrity of different brain functions. The 5-HT homeostasis is regulated by many factors, including serotonin transporter (SERT), monoamine oxidase enzyme (MAO), and several 5-HT receptors, including the 5-HT1B. There is little knowledge how the dynamics of this system is affected by the amyloid-β (Aβ) burden of Alzheimer's disease (AD) pathology. SH-SY5Y neuroblastoma cells transfected with the amyloid precursor protein (APP) gene containing the Swedish mutations causing familial AD (APPswe), were used as a model to explore the effect of Aβ pathology on 5-HT1B and related molecules including the receptor adaptor protein (p11), SERT and MAOA gene expression, and MAOA activity after treatment with selective serotonin reuptake inhibitor (SSRI) (sertraline), and a 5-HT1B receptor antagonist. Sertraline led more than 70 fold increase of 5-HT1B gene expression (p < 0.001), an increased serotonin turnover in both APPswe and control cells and reduced intracellular serotonin levels by 75% in APPswe cells but not in controls (p > 0.05). Treatment with the 5-HT1B receptor antagonist increased SERT gene-expression in control cells but not in the APPswe cells. 5-HT and 5-HT1B antagonist treatment resulted in different p11 expression patterns in APPswe cells compared to controls. Although MAOA gene expression was not changed by APPswe overexpression, adding 5-HT lead to a significant increase in MAOA gene expression in APPswe but not control cells. These findings suggest that the sensitivity of the 5-HT1B receptor and related systems is affected by APPswe overexpression, with potential relevance for pharmacologic intervention in AD. This may at least partly explain the lack of effect of SSRIs in patients with AD and depression.

%B J Alzheimers Dis %V 53 %P 349-61 %8 2016 May 07 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27163814?dopt=Abstract %R 10.3233/JAD-160046