Current Alzheimer Research - Volume 21, Issue 8, 2024

Apathy is a multidimensional and complex disease that is the primary neuropsychiatric symptom among those diagnosed with Alzheimer's disease (AD). Yet, apathy in AD is sometimes underestimated.

A systematic literature review was conducted using databases such as PubMed, Scopus, and Web of Science. The search utilized specific keywords related to apathy and Alzheimer's disease (e.g., “apathy,” “Alzheimer's disease,” “neuropsychiatric symptoms,” “front-striatal circuitry”). The studies were selected based on pre-defined criteria, including publication date (within the last 10 years), peer-reviewed status, and relevance to neurobiological, neurochemical, and behavioral aspects of apathy in AD. The articles were screened through title and abstract reviews, followed by full-text evaluations to ensure they met the inclusion criteria, such as relevance to apathy in Alzheimer's patients, study design rigor, and methodological quality.

Some research on the behavioral and neurobiological characteristics of apathy in AD points to the role of the front-striatal circuitry, particularly the anterior cingulate cortex (ACC). In addition, we reviewed the neurochemical, neuropsychological, and neuropathological characteristics believed to be associated with apathy symptoms.

The findings indicate that understanding the intricate neurobiological underpinnings of apathy in AD is crucial for developing targeted interventions. Our analysis suggests that a multimodal approach, incorporating both pharmacological and personalized non-pharmacological strategies, could enhance therapeutic efficacy and improve patient outcomes. This highlights the need for future research to explore these combined treatment modalities and their potential to alleviate apathy in AD patients.

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.

The potential relationship between Alzheimer's Disease (AD) and ferroptosis has received considerable attention, yet there is no comprehensive visualization analysis in this field. This study aimed to explore the research frontiers and hotspots through bibliometric analysis.

Literature related to AD and ferroptosis was collected from the Web of Science Core Collection. Data, including countries, authors, institutions, journals, and keywords, were analyzed by Tableau Public Desktop and Citespace software.

A total of 305 articles published between January 1^st, 2013, and December 31^st, 2023, were included, and the number of articles on the relationship between AD and ferroptosis has increased annually, with the largest number reported from China (162 articles). The articles from Professor SJ Dixon were cited most frequently. Among the top ten most cited articles, four were published in top journals. The University of Melbourne emerged as the institution with the highest number of publications (27 articles). Among the journals, most of the articles were published in Frontiers in Aging Neuroscience (13 articles, accounting for 4.26%). The co-occurrence analysis of keywords revealed that major hotspots in this field contained oxidative stress, cell death, and lipid peroxidation. Keyword burst analysis indicated that antioxidant was the term with the longest duration of high interest, while clustering analysis showed that this research area primarily focused on amyloid precursor protein, drug development, and diagnostic models.

Bibliometric analyses were conducted to comprehensively present the research progress and trends on the relationship between AD and ferroptosis, providing valuable evidence for future research in related fields.

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 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.