Physics of Life Reviews, Год журнала: 2023, Номер 48, С. 47 - 98
Опубликована: Дек. 12, 2023
Язык: Английский
Chemical Society Reviews, Год журнала: 2021, Номер 51(2), С. 513 - 565
Опубликована: Дек. 10, 2021
We discuss novel approaches for embracing and reproducing complexity of Tau pathology required developing disease-relevant diagnostics effective therapies.
Язык: Английский
Процитировано
117
Trends in Neurosciences, Год журнала: 2023, Номер 46(3), С. 176 - 198
Опубликована: Янв. 13, 2023
Neurological and psychiatric diseases have high degrees of genetic pathophysiological heterogeneity, irrespective clinical manifestations. Traditional medical paradigms focused on late-stage syndromic aspects these diseases, with little consideration the underlying biology. Advances in disease modeling methodological design paved way for development precision medicine (PM), an established concept oncology growing attention from other specialties. We propose a PM architecture central nervous system built four converging pillars: multimodal biomarkers, systems medicine, digital health technologies, data science. discuss Alzheimer's (AD), area significant unmet need, as case-in-point proposed framework. AD can be seen one most advanced PM-oriented models compelling catalyzer towards neuroscience drug healthcare practice.
Язык: Английский
Процитировано
70
Trends in Cognitive Sciences, Год журнала: 2023, Номер 27(9), С. 814 - 832
Опубликована: Июнь 5, 2023
Язык: Английский
Процитировано
55
National Science Review, Год журнала: 2024, Номер 11(5)
Опубликована: Фев. 27, 2024
ABSTRACT Virtual brain twins are personalized, generative and adaptive models based on data from an individual’s for scientific clinical use. After a description of the key elements virtual twins, we present standard model personalized whole-brain network models. The personalization is accomplished using subject’s imaging by three means: (1) assemble cortical subcortical areas in subject-specific space; (2) directly map connectivity into models, which can be generalized to other parameters; (3) estimate relevant parameters through inversion, typically probabilistic machine learning. We use healthy ageing five diseases: epilepsy, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease psychiatric disorders. Specifically, introduce spatial masks demonstrate their physiological pathophysiological hypotheses. Finally, pinpoint challenges future directions.
Язык: Английский
Процитировано
35
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Март 23, 2024
Abstract The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three age gaps (BAG) derived from gray matter volume (GM-BAG), white microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10 −8 ). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative neuropsychiatric disorders WM-BAG cancer therapy. displayed most pronounced heritability enrichment in variants within conserved regions. Oligodendrocytes astrocytes, but not neurons, exhibited notable WM FC-BAG, respectively. Mendelian randomization potential causal effects several chronic diseases on aging, such as type 2 diabetes AD WM-BAG. Our results provide insights into genetics with clinical implications lifestyle therapeutic interventions. All are publicly available at https://labs.loni.usc.edu/medicine .
Язык: Английский
Процитировано
24
Cerebral Cortex, Год журнала: 2024, Номер 34(3)
Опубликована: Март 1, 2024
Abstract Alzheimer’s disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies 20 AD studies. patients, compared controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior (PCC), right temporal lobes, left angular gyrus increased between DMN inferior gyrus. within mPFC/ACC precuneus/PCC occipital dorsolateral cortex. Conjunction analysis shared precuneus/PCC. Compared MCI, had lobes. share likely underpinning episodic memory deficits neuropsychiatric symptoms, differ alterations related impairments other domains such as language, vision, execution. This may throw light on neuropathological mechanisms two stages dementia.
Язык: Английский
Процитировано
19
Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)
Опубликована: Дек. 22, 2021
Abstract Selective autophagy is an evolutionarily conserved mechanism that removes excess protein aggregates and damaged intracellular components. Most eukaryotic cells, including neurons, rely on proficient mitophagy responses to fine-tune the mitochondrial number preserve energy metabolism. In some circumstances (such as presence of pathogenic oligopolymers mutations), dysfunctional leads nerve degeneration, with age-dependent accumulation organelles, leading neurodegenerative disease. However, when oligopolymers, mutations, stress, or injury are present, prevents mitochondria. Accordingly, mediates neuroprotective effects in forms disease (e.g., Alzheimer's disease, Parkinson’s Huntington's Amyotrophic lateral sclerosis) acute brain damage stroke, hypoxic–ischemic injury, epilepsy, traumatic injury). The complex interplay between neurological disorders suggests targeting might be applicable for treatment diseases injury. due complexity mechanism, can both harmful beneficial, future efforts should focus maximizing its benefits. Here, we discuss impact disorders, emphasizing contrast positive negative mitophagy.
Язык: Английский
Процитировано
91
Nature Reviews Neurology, Год журнала: 2022, Номер 19(2), С. 73 - 90
Опубликована: Дек. 20, 2022
Язык: Английский
Процитировано
55
Alzheimer s & Dementia, Год журнала: 2022, Номер 19(3), С. 749 - 760
Опубликована: Июнь 6, 2022
To test the utility of "A/T/N" system in Chinese population, we study core Alzheimer's disease (AD) biomarkers a newly established cohort.
Язык: Английский
Процитировано
54
Trends in Cognitive Sciences, Год журнала: 2023, Номер 27(3), С. 282 - 301
Опубликована: Янв. 30, 2023
Язык: Английский
Процитировано
38