AI Article Synopsis
- Mild Behavioral Impairment (MBI) in older adults without dementia is associated with a higher risk of cognitive decline but lacks comprehensive understanding of its underlying causes.
- Research indicates MBI is linked to structural and functional changes in the brain, genetic risk factors for Alzheimer's disease, and various types of brain pathology involving amyloid and tau proteins.
- Potential mechanisms connecting MBI to these pathologies include disruptions in hormones, neurotrophic factors, neuroinflammation, and neurotransmitter balance, which could inform targeted treatment approaches and future research.
Article Abstract
The emergence of sustained neuropsychiatric symptoms (NPS) among non-demented individuals in later life, defined as mild behavioral impairment (MBI), is linked to a higher risk of cognitive decline. However, the underlying pathophysiological mechanisms remain largely unexplored. A growing body of evidence has shown that MBI is associated with alterations in structural and functional neuroimaging studies, higher genetic predisposition to clinical diagnosis of Alzheimer's disease (AD), as well as amyloid and tau pathology assessed in the blood, cerebrospinal fluid, positron-emission tomography (PET) imaging and neuropathological examination. These findings shed more light on the MBI-related potential neurobiological mechanisms, paving the way for the development of targeted pharmacological approaches. In this review, we aim to discuss the available clinical evidence on the role of amyloid and tau pathology in MBI and the potential underlying pathophysiological mechanisms. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, disruption of neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), abnormal neuroinflammatory responses including the kynurenine pathway, dysregulation of transforming growth factor beta (TGF-β1), epigenetic alterations including micro-RNA (miR)-451a and miR-455-3p, synaptic dysfunction, imbalance in neurotransmitters including acetylcholine, dopamine, serotonin, gamma-aminobutyric acid (GABA) and norepinephrine, as well as altered locus coeruleus (LC) integrity are some of the potential mechanisms connecting MBI with amyloid and tau pathology. The elucidation of the underlying neurobiology of MBI would facilitate the design and efficacy of relative clinical trials, especially towards amyloid- or tau-related pathways. In addition, we provide insights for future research into our deeper understanding of its underlying pathophysiology of MBI, and discuss relative therapeutic implications.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11240615 | PMC |
| http://dx.doi.org/10.3390/cells13131164 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Proteomic Insight Into Alzheimer's Disease Pathogenesis Pathways.
Proteomics
January 2025
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alzheimer's disease (AD) is a leading cause of dementia, but the pathogenesis mechanism is still elusive. Advances in proteomics have uncovered key molecular mechanisms underlying AD, revealing a complex network of dysregulated pathways, including amyloid metabolism, tau pathology, apolipoprotein E (APOE), protein degradation, neuroinflammation, RNA splicing, metabolic dysregulation, and cognitive resilience. This review examines recent proteomic findings from AD brain tissues and biological fluids, highlighting potential biomarkers and therapeutic targets.
View Article and Find Full Text PDFAnti-neuroinflammatory and Neuroprotective Effects of T-006 on Alzheimer's Disease Models by Modulating TLR4-Mediated MyD88/ NF-κB Signaling.
CNS Neurol Disord Drug Targets
January 2025
School of Medicine, Foshan University, Foshan, 528000, China.
Introduction: Neuroinflammation derived from the activation of the microglia is considered a vital pathogenic factor of Alzheimer's Disease (AD). T-006, a tetramethylpyrazine derivative, has been found to alleviate cognitive deficits via inhibiting tau expression and phosphorylation in AD transgenic mouse models. Recently, T-006 has been proven to dramatically decrease the levels of total Amyloid β (Aβ) peptide and Glial Fibrillary Acidic Protein (GFAP) and suppress the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in APP/PS1 mice.
View Article and Find Full Text PDFRecent advancements in the therapeutic approaches for Alzheimer's disease treatment: current and future perspective.
RSC Med Chem
December 2024
Pharmaceutical Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Sciences Pilani Pilani Campus, Vidya Vihar Pilani 333031 RJ India +91 1596 244183 +91 1596 255 506.
Alzheimer's disease (AD) is a complex, incurable neurological condition characterized by cognitive decline, cholinergic neuron reduction, and neuronal loss. Its exact pathology remains uncertain, but multiple treatment hypotheses have emerged. The current treatments, single or combined, alleviate only symptoms and struggle to manage AD due to its multifaceted pathology.
View Article and Find Full Text PDFAssociation of Favorable Cerebrospinal Fluid Markers With Reversion of Mild Cognitive Impairment Due to Parkinson's Disease.
J Neuropsychiatry Clin Neurosci
January 2025
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
Objective: Cognitive impairment is a common nonmotor symptom among individuals with Parkinson's disease (PD). Although cognitive impairment generally develops progressively, individuals with PD-associated mild cognitive impairment (PD-MCI) may revert to being cognitively normal (CN), which is referred to as PD-MCI reversion. Previous studies are inconsistent in whether PD-MCI reverters are at greater risk for PD-MCI recurrence relative to CN individuals.
View Article and Find Full Text PDFPlasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.
Fluids Barriers CNS
January 2025
Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, 760 Press Ave, 124 HKRB, Lexington, KY, 40536-0679, USA.
Background: Blood-brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.
Methods: We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!