International Journal of Obesity, Год журнала: 2024, Номер 48(6), С. 841 - 848
Опубликована: Март 7, 2024
Язык: Английский
Alzheimer s & Dementia, Год журнала: 2023, Номер 19(12), С. 5860 - 5871
Опубликована: Авг. 31, 2023
Abstract With the increase in large multimodal cohorts and high‐throughput technologies, potential for discovering novel biomarkers is no longer limited by data set size. Artificial intelligence (AI) machine learning approaches have been developed to detect interactions complex sets. We discuss exemplar uses evaluate current applications limitations of AI discover biomarkers. Remaining challenges include a lack diversity sets available, sheer complexity investigating interactions, invasiveness cost some biomarkers, poor reporting studies. Overcoming these will involve collecting from underrepresented populations, developing more powerful approaches, validating use noninvasive adhering guidelines. By harnessing rich through international collaborative innovation, we are well positioned identify clinically useful that accurate, generalizable, unbiased, acceptable clinical practice. Highlights may accelerate dementia biomarker discovery. suitability due size bias cohort selection. Multimodal data, diverse sets, improved real‐world validation, interdisciplinary collaboration required.
Язык: Английский
Процитировано
45
Nature reviews. Immunology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 9, 2024
Язык: Английский
Процитировано
16
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14499 - 14499
Опубликована: Сен. 24, 2023
Over the past 30 years, majority of (pre)clinical efforts to find an effective therapy for Alzheimer’s disease (AD) focused on clearing β-amyloid peptide (Aβ) from brain since, according amyloid cascade hypothesis, was (and it is still considered by many) pathogenic determinant this neurodegenerative disorder. However, as reviewed in article, results numerous clinical trials that have tested anti-Aβ therapies date indicate plays a minor role pathogenesis AD. Indeed, even Aducanumab and Lecanemab, two antibodies recently approved FDA AD therapy, well Donanemab showed limited efficacy cognitive parameters phase III trials, despite their capability markedly lowering Aβ load. Furthermore, preclinical evidence demonstrates possesses several physiological functions, including memory formation, suggesting may part be due loss function peptide. Finally, generally accepted could result many molecular dysfunctions, therefore, if we keep chasing only Aβ, means cannot see forest trees.
Язык: Английский
Процитировано
33
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 11955 - 11955
Опубликована: Ноя. 7, 2024
Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent conditions that present considerable public health issue in aging populations worldwide. Recent research has proposed a novel conceptualization of AD as "type 3 diabetes", highlighting the critical roles insulin resistance impaired glucose metabolism pathogenesis disease. This article examines implications this association, exploring potential new avenues for treatment preventive strategies AD. Key evidence linking to emphasizes metabolic processes contribute neurodegeneration, including inflammation, oxidative stress, alterations signaling pathways. By framing within context, we can enhance our understanding its etiology, which turn may influence early diagnosis, plans, measures. Understanding manifestation opens up possibility employing therapeutic incorporate lifestyle modifications use antidiabetic medications mitigate cognitive decline. integrated approach improve patient outcomes deepen comprehension intricate relationship between neurodegenerative diseases disorders.
Язык: Английский
Процитировано
11
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Сен. 9, 2024
Язык: Английский
Процитировано
8
Life, Год журнала: 2025, Номер 15(1), С. 96 - 96
Опубликована: Янв. 14, 2025
Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer's disease (AD). Although the biological mechanisms underlying these associations remain unclear, role of periodontal pathogens, Porphyromonas gingivalis, has garnered significant attention. P. a major driver is recognized for its potential effects putative in AD pathogenesis. This review examines evidence connecting gingivalis to hallmark features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, other neuropathological features consistent with AD. Virulence factors, gingipains lipopolysaccharides, were shown be implicated blood-brain barrier disruption, neuronal damage. gingivalis-derived outer membrane vesicles may serve disseminate virulence factors brain tissues. Indirect mechanisms, inflammation triggered by chronic infections, are also supposed exacerbate neurodegenerative processes. While exact pathways uncertain, studies detecting components AD-affected brains support their possible underscores need further investigation into gingivalis-mediated interplay host responses. Understanding interactions could provide critical insights novel strategies reducing risk through management.
Язык: Английский
Процитировано
1
Nature Reviews Neurology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 4, 2025
Язык: Английский
Процитировано
1
Nature Mental Health, Год журнала: 2024, Номер 2(1), С. 25 - 40
Опубликована: Янв. 10, 2024
Язык: Английский
Процитировано
6
Current Opinion in Neurology, Год журнала: 2024, Номер 37(2), С. 154 - 165
Опубликована: Янв. 18, 2024
Purpose of review Genetics studies provide important insights into Alzheimer disease (AD) etiology and mechanisms. Critical advances have been made recently, mainly thanks to the access novel techniques larger studies. Recent findings In monogenic AD, progress has with a better understanding mechanisms associated pathogenic variants input clinical in presymptomatic individuals. complex increasing sample sizes both DNA chip-based (genome-wide association studies, GWAS) exome/genome sequencing case-control unveiled common rare risk factors, while their combined effect starts suggest existence families oligogenic inheritance early-onset, nonmonogenic, AD. Summary Most genetic factors known consequence designate aggregation Aβ peptide as core etiological factor AD thus confirming that research based on – where amyloid cascade seems more straightforward is relevant well. Novel mechanistic unveiling attempting combine will offer promising perspectives for future prevention, at least regarding early-onset probably case later onset
Язык: Английский
Процитировано
6
Journal of Alzheimer s Disease, Год журнала: 2024, Номер 98(4), С. 1199 - 1218
Опубликована: Март 19, 2024
Animal models, particularly transgenic mice, are extensively used in Alzheimer's disease (AD) research to emulate key hallmarks, such as amyloid plaques and neurofibrillary tangles formation. Although these models have contributed our understanding of AD pathogenesis can be helpful testing potential therapeutic interventions, their reliability is dubious. While preclinical studies shown promise, clinical trials often yield disappointing results, highlighting a notable gap disparity between animal human pathology. Existing frequently overlook early-stage pathologies other characteristics, thereby limiting application identifying optimal interventions. Enhancing model necessitates rigorous study design, comprehensive behavioral evaluations, biomarker utilization. Overall, nuanced each model's neuropathology, its fidelity AD, limitations essential for accurate interpretation successful translation findings. This article analyzes the discrepancies pathology that complicate findings from applications. We also delve into attributes propose new perspective on this deliberate over primary experimental models. Additionally, we discuss several fundamental problems may explain translational failures suggest some possible directions more effective studies.
Язык: Английский
Процитировано
6