Current Alzheimer Research - Online First

Alzheimer's disease is a chronic brain disease that includes memory and language disorders. This disease, which is considered the most common cause of dementia worldwide, accounts for 60-80% of all dementia cases. Recent studies suggest that the cerebellum may play a role in cognitive functions as well as motor functions.

The study was conducted on 40 Alzheimer's patients and 40 healthy individuals. In our study, volumetric evaluation of the cerebellum was performed.

As expected, significant differences were found in cerebellar volume reduction in AD patients compared to healthy controls. Significant volume increase was observed in some regions of the cerebellum in Alzheimer's patients compared to healthy individuals.

The findings supported the role of the cerebellum in cognitive functions. Volume reductions may assist clinicians in making an early diagnosis of AD.

The lack of effective therapy for the treatment of Alzheimer's disease demands both the search for new drugs and the reconsideration of already known substances currently used in other areas of medicine. Drosophila melanogaster offers the potential to model features of Alzheimer's disease, study disease mechanisms, and conduct drug screening.

The purpose of this work was to analyze the neuroprotective properties of the drug “carnicetine”, which is an acetylated form of the natural low molecular weight compound L-carnitine. The drug is able to cross the blood-brain barrier and is currently used as a means of improving cellular metabolism.

Using tissue-specific drivers, direct expression of amyloid beta peptide (42 amino acids) was exhibited in certain groups of neurons in the Drosophila melanogaster brain, namely in dopaminergic and cholinergic neurons. The effect of acetyl-L-carnitine (carnicetine) on the death of these neurons and the memory of flies was analyzed.

The expression of amyloid beta peptide in dopaminergic or cholinergic neurons resulted in neurodegeneration of cholinergic neurons in the Drosophila brain and memory impairment. The use of carnicetine added to animal food made it possible to treat these disorders. At the same time, no effect on dopaminergic neurons was noted.

The data obtained confirmed the neuroprotective properties of the drug under study, demonstrating its participation in the restoration of the cholinergic system and the feasibility of using carnicetine for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of Flemingia vestita (FV) phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment.

Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes.

8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions.

The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology.

8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD.

The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD.

To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts.

Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks.

This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.