Current Progress and Future Directions in Non-Alzheimer’s Disease Tau PET Tracers

ACS Chemical Neuroscience, Год журнала: 2025, Номер 16(2), С. 111 - 127

Опубликована: Янв. 6, 2025

Alzheimer's disease (AD) and non-AD tauopathies are dominant public health issues driven by several factors, especially in the aging population. The discovery of first-generation radiotracers, including [18F]FDDNP, [11C]PBB3, [18F]flortaucipir, [18F]THK series, for vivo detection has marked a significant breakthrough fields neuroscience radiopharmaceuticals, creating robust new category labeled compounds: tau positron emission tomography (PET) tracers. Subsequently, other PET tracers with improved binding properties have been developed using various chemical scaffolds to target three-repeat/four-repeat (3R/4R) folds AD. In 2020, [18F]flortaucipir was approved U.S. Food Drug Administration imaging pathology adult patients cognitive deficits undergoing evaluation Despite remarkable progress development AD tracers, agents rare (4R [predominantly expressing 4R isoform], involved progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, globular glial tauopathy, 3R such as Pick's disease) remain substantially underdeveloped. this review, we discuss recent tracer development, particular emphasis on clinically validated their potential use tauopathies. Additionally, highlight critical need further specifically designed tauopathies, an area that remains significantly underexplored despite its importance advancing understanding diagnosis these disorders.

Язык: Английский

---

The Role of TNF-α in Alzheimer’s Disease: A Narrative Review

Cells, Год журнала: 2023, Номер 13(1), С. 54 - 54

Опубликована: Дек. 26, 2023

This review analyzes the role of TNF-α and its increase in biological fluids mild cognitive impairment, Alzheimer’s disease (AD). The potential inhibition with pharmacological strategies paves way for preventing AD improving function people at risk dementia. We conducted a narrative to characterize evidence relation involvement possible therapeutic inhibition. Several studies report that patients RA systemic inflammatory diseases treated blocking agents reduce probability emerging dementia compared general population. Animal model also showed interesting results are discussed. An increasing amount basic scientific data clinical underscore importance processes subsequent glial activation pathogenesis AD. targeted therapy is biologically plausible approach cognition preservation further trials necessary investigate benefits populations developing

Язык: Английский

---

Unraveling Alzheimer’s: the promise of aducanumab, lecanemab, and donanemab

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Год журнала: 2024, Номер 60(1)

Опубликована: Июнь 14, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative condition that causes cognitive decline, memory loss, and reduced personal autonomy. The pathology of AD involves the aggregation abnormal brain proteins, specifically beta-amyloid plaques tau tangles, disrupting neuronal communication leading to loss cells. Aducanumab, monoclonal antibody, demonstrates promise in clinical trials by selectively binding aggregated amyloid-beta, notable decrease plaque burden potential benefits. However, regulatory approval for aducanumab remains controversial. Lecanemab donanemab are recent additions AD’s treatment landscape, both targeting amyloid-beta. shares similarities with its mechanism action, while employs distinct approach specific truncated form Positive outcomes have been observed early-stage drugs, demonstrating reduction amyloid-beta plaques. While aducanumab’s offers hope treatment, ongoing studies on lecanemab imperative comprehensive understanding their modification. Here, we show this review treatments, focus primary action ultimately giving broader insight topic. emphasizes necessity long-term efficacy safety data assess overall impact these drugs decline functional future researchers endeavor. In conclusion, development antibodies represents significant stride demanding further investigation ascertain true role therapeutic arsenal challenging condition.

Язык: Английский

---

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2645 - 2645

Опубликована: Фев. 24, 2024

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture underlying neurobiological mechanisms NPSs at preclinical stages cognitive decline Alzheimer's disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident is defined by emergence persistent among non-demented individuals later life. These include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception thought content, social inappropriateness. Accumulating evidence has recently begun to shed more light on background MBI, focusing its potential association with factors related AD. Apolipoprotein E (APOE) genotype MS4A locus associated ZCWPW1 inappropriateness psychosis, BIN1 EPHA1 NME8 apathy. between MBI polygenic risk scores (PRSs) terms AD also explored. Potential implicated neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, immune responses. In this review, we summarize critically discuss available emphasis AD, aiming gain insights into mechanisms, which till now unexplored. addition, propose future areas research emerging field, aim better understand molecular links decline.

Язык: Английский

---

Uncovering the intricacies of IGF-1 in Alzheimer’s disease: new insights from regulation to therapeutic targeting

Inflammopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Язык: Английский

---

Updates and future perspectives on neuropsychiatric symptoms in Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(3)

Опубликована: Март 1, 2025

Abstract Neuropsychiatric symptoms (NPS) are common throughout the Alzheimer's disease (AD) continuum and profoundly affect patients, caregivers, health‐care systems. This review synthesizes key research presented in 2022 2023 Association International Society to Advance Research Treatment Syndromes–Professional Interest Area (NPS‐PIA) Year‐In‐Reviews, emphasizing six critical areas: (1) diversity disparities, (2) diagnostic frameworks, (3) neurobiology of NPS, (4) NPS as a marker, (5) impact COVID‐19, (6) interventions. accelerates AD progression, increases functional decline, diminishes quality life, heightens caregiver burden institutionalization rates. Current treatments primarily rely on psychotropics, which offer limited efficacy raise safety concerns. aims inform clinicians researchers about recent advancements while identifying gaps for future studies improve outcomes individuals with AD. Highlights disease–related neuropsychiatric has rapidly increased, indicating heightened interest. Key areas include: diversity, diagnostics, markers, COVID‐19 impact, treatments. A road map studies, based research, is provided. includes considerations study applicability validity.

Язык: Английский

---

Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review

Antioxidants, Год журнала: 2024, Номер 13(9), С. 1062 - 1062

Опубликована: Авг. 30, 2024

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration structure and function nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's (AD), Huntington's (HD), Amyotrophic lateral sclerosis (ALS), Multiple (MS), often lead to severe cognitive motor deficits. A critical component neurodegenerative pathologies is imbalance between pro-oxidant antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption lipid-rich environment make it particularly vulnerable damage. Pro-oxidants such as reactive nitrogen species (RNS) (ROS) are continuously generated during normal metabolism, counteracted enzymatic non-enzymatic defenses. In diseases, this balance disrupted, leading neuronal This systematic review explores roles stress, gut microbiota, epigenetic modifications aiming elucidate interplay these factors identify potential therapeutic strategies. We conducted comprehensive search articles published 2024 across major databases, focusing on studies examining relationships redox homeostasis, changes neurodegeneration. total 161 were included, comprising clinical trials, observational studies, experimental research. Our findings reveal that stress plays central role pathogenesis with microbiota composition significantly influencing balance. Specific bacterial taxa markers identified modulators suggesting novel avenues for intervention. Moreover, recent evidence from human animal supports emerging concept targeting homeostasis through therapies. Future research should focus validating targets settings exploring personalized medicine strategies based individual profiles.

Язык: Английский

---

Effects of a dual intervention (motor and virtual reality-based cognitive) on cognition in patients with mild cognitive impairment: a single-blind, randomized controlled trial

Journal of NeuroEngineering and Rehabilitation, Год журнала: 2024, Номер 21(1)

Опубликована: Авг. 1, 2024

Abstract Background The increase in cases of mild cognitive impairment (MCI) underlines the urgency finding effective methods to slow its progression. Given limited effectiveness current pharmacological options prevent or treat early stages this deterioration, non-pharmacological alternatives are especially relevant. Objective To assess a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity daily living (ADL) functions and impact depression ability perform such activities patients with MCI. Methods Thirty-four older adults (men, women) MCI were randomized experimental group ( n = 17; 75.41 ± 5.76) control 77.35 6.75) group. Both groups received motor training, through aerobic, balance resistance Subsequently, training VR, while traditional training. Cognitive functions, depression, (ADLs) assessed using Spanish versions Montreal Assessment (MoCA-S), Short Geriatric Depression Scale (SGDS-S), Instrumental Activities Daily Living (IADL-S) before after 6-week (a total twelve 40-minutes sessions). Results Between comparison did not reveal significant differences either function geriatric depression. intragroup effect was both p < 0.001), large sizes. There no statistically improvement any when evaluating their performance ADLs (control, 0.28; experimental, 0.46) as expected. completion rate higher (82.35%) compared (70.59%). Likewise, participants reached level difficulty application needed less time complete task at each level. Conclusions dual intervention, prior Immersive VR shown be beneficial strategy improve reduce Similarly, benefited from improvements. Trial registration ClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931 .

Язык: Английский

---

Monoamine alterations in Alzheimer’s disease and their implications in comorbid neuropsychiatric symptoms

GeroScience, Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Язык: Английский

---

The Relationship Between Antipsychotics, Cognitive Enhancers, and Major Adverse Cardiovascular/Cerebrovascular Events (MACCE) in Older Adults with Behavioral and Psychological Symptoms of Dementia

Drugs & Aging, Год журнала: 2024, Номер 41(10), С. 847 - 858

Опубликована: Авг. 9, 2024

Antipsychotics and cognitive enhancers are often used to treat psychosis behavioral disturbances in individuals with dementia; however, these drugs have been linked various adverse events including both metabolic cerebro/cardiovascular events. Thus, this study sought estimate the risk of major cardiovascular/cerebrovascular (MACCE) across four psychological symptoms dementia (BPSD) treatment models by exploring potential associations between antipsychotics (APs), cognitive-enhancing medications, dosage, earlier MACCE onset. Patients were obtained from Loma Linda University Medical Center database who age ≥ 50 or older diagnosed BPSD symptoms. Treatment group drug dosing analyzed using Cox regression analyses predict time until Patient at diagnosis, sex, smoking status, race/ethnicity, previous diagnoses included as covariate variables. The final population consisted 1162 individuals. Results indicated a significant effect medication type on duration MACCE, (p < 0.001), odds experiencing being 96.3% higher for treated APs 0.001). There was also AP dosage 0.001) enhancer sooner 238% those high doses 76% 0.010). use associated greatest an medical outcome adults concurrent Use medications should include close monitoring

Язык: Английский

---