CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimers disease as an indicator of tau phosphorylation

Abstract Background Recently, several studies suggested potential involvements of α-synuclein in Alzheimers disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. Methods In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinsons disease, and 32 healthy control (HC) were collected. CSF amyloid-β1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. Results CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinsons disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-β1-42/phosphorylated tau181ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-β1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimers disease pathophysiology, all A−T+N+ patients with N/αS+ were reintegrated into AD. Conclusions The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders

Cognitive functions and stereopsis in patients with Parkinson's disease and Alzheimer's disease using 3-dimensional television: a case controlled trial.

Stereopsis or depth perception is an awareness of the distances of objects from the observer, and binocular disparity is a necessary component of recognizing objects through stereopsis. In the past studies, patients with neurodegenerative disease (Alzheimer dementia, AD; Parkinson's disease IPD) have problems of stereopsis but they did not have actual stimulation of stereopsis. Therefore in this study, we used a 3-dimensional (3D) movie on 3D television (TV) for actual stereopsis stimulation. We propose research through analyzing differences between the three groups (AD, IPD, and Controls), and identified relations between the results from the Titmus Stereo Fly Test, and the 3D TV test. The study also looked into factors that affect the 3D TV test. Before allowing the patients to watch TV, we examined Titmus stereo Fly Test and cognitive test. We used the 3D version of a movie, of 17 minutes 1 second duration, and carried out a questionnaire about stereopsis. The scores of the stereopsis questionnaire were decreased in AD patients, compared with in IPD and controls, although they did not have any difference of Titmus Stereo Fly Test scores. In IPD patients, cognitive function (Montreal cognitive assessment, MoCA) scores were correlated with the scores of the stereopsis questionnaire. We could conclude that Titmus fly test could not distinguish between the three groups and cognitive dysfunction contributes to actual stereopsis perception in IPD patients. Therefore the 3D TV test of AD and IPD patients was more effective than Titmus fly test

Effectiveness and Complications of Bone Marrow Aspirate Concentrate in Patients with Knee Osteoarthritis of Kellgren–Lawrence Grades II–III

This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren–Lawrence (K–L) grades II–III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K–L grades II–III OA. The exclusion criteria were age of 80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6–8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up (p p p < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K–L grades II–III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection

Associated results of the Titmus Stereo Fly Test, in idiopathic Parkinson disease patients, Alzheimer’s disease patients, and Controls.

<p>IPD: Idiopathic Parkinson’s disease, AD: Alzheimer’s disease.</p><p>Associated results of the Titmus Stereo Fly Test, in idiopathic Parkinson disease patients, Alzheimer’s disease patients, and Controls.</p

Correlations of stereopsis questionnaire scores, and Age, MoCA and the Titmus stereo Fly Test.

<p>AD: Alzheimer’s disease, IPD: Idiopathic Parkinson’s disease.</p><p>Total: IPD+AD+Controls, Montreal cognitive assessment</p><p>* p<0.05</p><p>**p<0.01</p><p>Correlations of stereopsis questionnaire scores, and Age, MoCA and the Titmus stereo Fly Test.</p

The number of patients, according to stereopsis questionnaire scores, in three groups.

<p>IPD: Idiopathic Parkinson’s disease, AD: Alzheimer’s disease.</p

The number of patients, according to the Titmus stereo Fly Test, in three groups.

<p>IPD: Idiopathic Parkinson’s disease, AD: Alzheimer’s disease.</p

Automated Subfield Volumetric Analysis of Hippocampus in Patients with Drug-Naïve Nondementia Parkinson’s Disease

Several studies used automated segmentation of hippocampal subfield (ASHS) for detailed measurements of anatomic subregions of the hippocampus, especially in the field of neurodegenerative disorders. In this study, we investigated the hippocampal subfield volume of patients with early-stage nondementia PD compared with normal healthy subjects using the ASHS method. A total of 32 subjects were enrolled in this study (sixteen patients with drug naive nondementia PD and sixteen healthy controls). All subjects were scanned with a 1.5 tesla MRI. The volumes of the seven subfields were calculated separately, and then, the whole hippocampal volume was calculated by the summing of CA1, CA2-3, CA4-DG, subiculum, presubiculum, and fimbria, excluding the hippocampal fissure. There were significant diagnosis-by-hemisphere interactive effects on the total hippocampal volume (F = 5.197; p=0.031) and the subfield volume of CA2-3 (F = 7.586; p=0.010) and CA4-DG (F = 7.403; p=0.011). The volumes of CA2-3 (F = 19.911; p<0.001), CA4-DG (F = 20.273; p<0.001), and total hippocampus (F = 10.573; p=0.005) in the left hemisphere were reduced compared to the right hemisphere. We suggest that the hippocampal volume asymmetry, especially in CA4-DG and CA2-3, could be observed in drug-naïve PD patients even in the early stage of the disease

Demographics, clinical data of idiopathic Parkinson disease patients, Alzheimer’s disease patients, and Controls.

<p>NS: Not significant, NA: Not analyzed, AD: Alzheimer’s disease, IPD: Idiopathic Parkinson’s disease.</p><p>* Statistical tests: ANOVA</p><p>^a: IPD vs AD</p><p>^b: IPD vs Controls</p><p>^c: AD vs Controls</p><p>Demographics, clinical data of idiopathic Parkinson disease patients, Alzheimer’s disease patients, and Controls.</p