Current Alzheimer Research - Volume 22, Issue 5, 2025

This study seeks to examine the relationship between cerebrospinal fluid (CSF) biomarkers (Aβ1-42, Phospho-Tau181p, Total-Tau) and brain volumetric changes measured by Brain Shift Integral (BSI) in Alzheimer's disease (AD) spectrum. We explore the potential of BSI as a complementary, non-invasive tool for early diagnosis and progression monitoring of AD.

AD is a neurodegenerative disorder marked by amyloid plaques and tau tangles, leading to cognitive decline. CSF biomarkers are key indicators of AD pathology, but their integration with imaging metrics like BSI could enhance early diagnosis. BSI quantifies brain volume changes via MRI, offering valuable insights into neurodegeneration across the AD spectrum.

The current study explores the use of BSI and CSF biomarkers for the early detection of Alzheimer’s disease.

This study utilized data from the ADNI database, including CSF biomarkers (Aβ1-42, t-tau, p- tau181) and BSI measurements from baseline and month 24 visits. Spearman correlations were performed to assess associations between biomarkers and brain volumetric changes. Linear regression models were used to examine the predictive value of biomarkers on BSI, controlling for potential confounders.

A total of 239 participants were included in the study, comprising 94 cognitively normal (CN) individuals, 104 with mild cognitive impairment (MCI), and 41 with AD. Significant negative correlations were observed between Aβ1-42 and both BBSI and VBSI in MCI at baseline (p=0.013) and 24 months (p=0.018), as well as between Aβ1-42 and VBSI in CN at baseline (p=0.039) and 24 months (p=0.033). In MCI, p-tau181 was positively correlated with BBSI (p=0.013) and VBSI (p=0.030) at baseline and with BBSI at 24 months (p=0.013). Linear regression analysis confirmed that Aβ1-42 and p-tau181 significantly predicted BSI measures in MCI (R²=0.141–0.173, p<0.05), while Aβ1-42 was a significant predictor of VBSI in CN (R²=0.156–0.166, p<0.01). No significant associations were found in AD.

This study underscores the role of CSF biomarkers—particularly Aβ1-42 and p-tau181—in detecting early brain atrophy across the Alzheimer’s disease spectrum, with limited utility in advanced stages. The findings highlight the importance of early intervention and support the integration of CSF biomarkers and BSI as diagnostic tools for monitoring disease progression and staging.

The application of the BSI is pivotal for monitoring brain volume alterations and their association with CSF biomarkers.

Alzheimer’s disease is associated with dysfunction of the cholinergic system, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) a promising therapeutic approach.

This study aimed to evaluate the neuroprotective effects and toxicity of essential oil (EO) and carlina oxide from Carthamus caeruleus in mice, assessing their potential for Alzheimer’s disease treatment.

The chemical composition of the essential oil extracted from the roots of Carthamus caeruleus was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The main component, carlina oxide, was isolated via column chromatography. The inhibitory activities of AChE and BChE were evaluated in vitro for both the essential oil and carlina oxide. Additionally, in vivo, toxicity was assessed in laboratory mice.

Chemical analysis identified carlina oxide (81.6%) as the major constituent, along with minor compounds such as 13-methoxycarlin oxide and hexadecanoic acid. Both the essential oil and its main component, carlina oxide, exhibited significant inhibitory activity against AChE and BChE, enzymes associated with Alzheimer’s disease. The essential oil demonstrated promising IC50 values, with stronger anti-BChE activity compared to the reference drug, galantamine. Toxicity tests in mice revealed no adverse effects at lower doses (0.2-0.5 g/kg). However, higher doses (1.0-2.0 g/kg) resulted in mild to significant toxicity, including weight loss and mortality.

The essential oil and carlina oxide demonstrated potent BChE inhibition, particularly relevant in advanced Alzheimer's disease. While effective at low doses, signs of toxicity were observed at higher concentrations, highlighting the importance of dose optimization. These findings suggest that C. caeruleus may serve as a natural source of cholinesterase inhibitors, pending further in vivo studies and clinical validation.

Carthamus caeruleus essential oil and carlina oxide show promising inhibitory effects on AChE and BChE, suggesting their potential as neuroprotective agents. However, their toxicity at higher doses highlights the need for cautious use and further investigation.

Behavioral and Psychological Symptoms of Dementia (BPSD) pose significant challenges for individuals with dementia and their caregivers. Agitation symptoms, in particular, present a complex management dilemma as there is a lack of consensus regarding pharmacotherapy, specifically with respect to the controversial use of valproate formulations. This study aims to assess the effectiveness of valproate treatment in addressing BPSD, with a specific focus on managing agitation symptoms in individuals with dementia.

A retrospective analysis was conducted at Peking Union Medical College Hospital (PUMCH) on patients diagnosed with BPSD who received valproate formulations between 2013 and 2023. Patients were classified into 'effective,' 'ineffective,' and 'unknown' groups based on their response to valproate treatment, and the distribution of BPSD symptoms between the effective and ineffective groups was compared.

Among the 116 patients studied, 62.1% exhibited effective responses, 12.1% showed ineffectiveness, and 25.9% had uncertain outcomes with valproate therapy. While the effective group displayed a higher prevalence of agitation symptoms and other behaviors like wandering, restricted and repetitive behaviors, and sleep disturbances compared to the ineffective group, these differences did not reach statistical significance (p = 0.156, 1.000, 0.899, 0.283). Patients in the ineffective group were more likely to experience aggression with comorbid psychotic symptoms compared to those in the effective group (p = 0.023).

Valproate may benefit agitation-predominant BPSD without psychosis. Discrepancies in prior findings may stem from differing dosing strategies. Its limited efficacy in psychosis-related aggression underscores the need for careful clinical evaluation.

The findings suggest that tailored valproate treatment at low doses may be beneficial in managing agitation without psychosis in Asian BPSD patients. Further validation through randomized controlled trials is essential to substantiate these observations.

Quinolinic Acid (QA), a neurotoxic metabolite in the kynurenine pathway, contributes to neuronal damage, oxidative stress, and neuroinflammation, playing a key role in Alzheimer's Disease (AD) pathogenesis. This study investigates the neuroprotective potential of polyphenolic compounds, particularly lycopene and a Curcumin-Zinc (Cur-Zn) complex, using in-silico and in-vitro approaches targeting the kynurenine pathway.

This study evaluated the neuroprotective potential of lycopene and Cur-Zn complex using in-silico and in-vitro approaches. Molecular docking was performed to assess their binding affinities with the kynurenine pathway enzymes, and in-vitro neuroprotection assays on N2a cells measured their efficacy against QA-induced oxidative stress.

Docking analysis revealed strong binding affinities of Cur-Zn and lycopene to IDO1 and KMO, with fitness scores of 143.11 and 126.41, respectively, indicating their potential as enzyme-specific inhibitors. Lycopene exhibited the most potent neuroprotective effect (IC50 = 0.63 µM), followed by Cur-Zn (1.59 µM). Both compounds significantly reduced QA-induced ROS levels, as confirmed by DCFDA fluorescence imaging. Additionally, they upregulated KAT and QPRT enzymes, promoting neuroprotective metabolite production.

Lycopene and Cur-Zn effectively modulate key kynurenine pathway enzymes while mitigating oxidative stress, supporting their potential as neuroprotective agents. Although bisabolol and bromelain exhibited some efficacy, their effects were comparatively lower.

Lycopene and Cur-Zn are promising candidates for AD therapy, demonstrating not only anti-oxidant activity but also a capacity to minimise the neurotoxic effects of QA, offering a dual mechanism of action. Further, in-vivo studies are needed to validate their therapeutic potential in neurodegenerative diseases.

The aim of this study was to assess the relationship between serum biomarkers of vascular dysfunction and neuropsychological performance in Alzheimer’s disease (AD) patients.

In this cross-sectional observational study, outpatients with AD who were referred to the Neuropsychiatry Clinic of the Eginition Hospital in Athens from January 2006 to December 2006 were consecutively enrolled. All the participants underwent a neuropsychological assessment.

The serum concentrations of Apolipoprotein A1 (ApoA1), Vascular Cell Adhesion Molecule 1 (VCAM-1), Intercellular Adhesion Molecule 1 (ICAM-1), Lipoprotein-A (LpA), and C-Reactive Protein (CR-P) were determined.

Fifty-six AD patients were enrolled. ApoA1 was correlated with Mini Mental State Examination (MMSE) and AD Cooperative Study-Activities of Daily Living (ADCS-ADL). Combined biomarkers were correlated with MMSE, Neuropsychiatry Inventory, Clinical Dementia Rating Scale, and ADCS-ADL.

Our study highlights the association between serum biomarkers of vascular dysfunction-specifically ApoA1, VCAM-1, ICAM-1, LpA, and CRP-and the cognitive and behavioral features of Alzheimer’s Disease.

These findings suggest that assessing vascular biomarkers may offer valuable insights into the pathophysiological mechanisms underlying cognitive and behavioral decline in AD.