Recent studies in Alzheimer's disease (AD) research have focused on various therapeutic approaches and biomarkers. A randomized controlled trial by Rajji et al. evaluated the efficacy of escitalopram for treating agitation in AD, finding it ineffective and associated with cardiac risks (ref: Rajji doi.org/10.1038/s41591-025-03569-y/). In contrast, Rash et al. conducted a phase 2a trial on laromestrocel, a mesenchymal stem cell therapy, which aimed to slow clinical progression and neuroinflammation in mild AD. Although the study design was robust, the results regarding efficacy remain inconclusive (ref: Rash doi.org/10.1038/s41591-025-03559-0/). Furthermore, Grande et al. explored blood-based biomarkers, identifying elevated levels of p-tau181, p-tau217, NfL, and GFAP as significant predictors of AD dementia, with strong predictive performance for 10-year outcomes (ref: Grande doi.org/10.1038/s41591-025-03605-x/). These findings highlight the potential of blood biomarkers in early detection and monitoring of AD progression. Additionally, Bateman et al. reported on the long-term safety and efficacy of gantenerumab in dominantly inherited AD, noting that the study was halted early due to regulatory issues, which limited the data on treatment outcomes (ref: Bateman doi.org/10.1016/S1474-4422(25)00024-9/). Ali et al. utilized multi-cohort cerebrospinal fluid proteomics to identify 2,173 dysregulated analytes across the AD continuum, emphasizing the importance of CSF analysis in understanding AD pathophysiology (ref: Ali doi.org/10.1016/j.neuron.2025.02.014/). The role of TDP-43 in neurodegeneration was also examined, with Rummens and Scialò revealing mechanisms of TDP-43 aggregation and its implications for sporadic TDP-43 proteinopathies (ref: Rummens doi.org/10.1016/j.neuron.2025.03.004/; Scialò doi.org/10.1016/j.neuron.2025.03.008/). Lastly, Franzmeier et al. highlighted the exacerbating effect of alpha-synuclein co-pathology on tau accumulation in AD, suggesting a need for integrated approaches in AD research (ref: Franzmeier doi.org/10.1186/s13024-025-00822-3/).

Research on amyotrophic lateral sclerosis (ALS) has revealed critical insights into its pathogenesis and potential therapeutic strategies. Zelic et al. utilized single-nucleus RNA sequencing to identify glial state changes in ALS, highlighting the role of inflammatory RIPK1 signaling in disease progression (ref: Zelic doi.org/10.1016/j.immuni.2025.02.024/). Cheng et al. focused on mitochondrial respiratory complex IV deficiency, noting that approximately half of sporadic ALS cases exhibit this defect, suggesting a common pathway in ALS pathology (ref: Cheng doi.org/10.1038/s41593-025-01896-4/). The HEALEY ALS platform trial provided insights into the efficacy of verdiperstat and pridopidine, with findings indicating limited effectiveness in slowing disease progression (ref: Verdiperstat doi.org/10.1001/jamaneurol.2024.5249/; Pridopidine doi.org/10.1001/jama.2024.26429/). Additionally, Coughlan et al. conducted a meta-analysis examining sex differences in tau-PET imaging in preclinical AD, revealing that female sex is associated with faster tau accumulation in certain brain regions, which may have implications for understanding cognitive decline in ALS patients (ref: Coughlan doi.org/10.1001/jamaneurol.2025.0013/). Chen et al. explored maternal behavior's impact on resilience to stress in mice, linking early life experiences to neuroinflammatory responses that could influence ALS susceptibility (ref: Chen doi.org/10.1038/s41467-025-57810-w/). These studies collectively underscore the multifaceted nature of ALS, integrating genetic, environmental, and neuroinflammatory factors in understanding disease mechanisms.

Parkinson's disease (PD) research has advanced our understanding of the molecular mechanisms underlying the disease. Callegari et al. elucidated the structure of human PINK1 at mitochondrial translocase complexes, providing insights into how mutations in PINK1 contribute to early-onset PD (ref: Callegari doi.org/10.1126/science.adu6445/). Winkler et al. discussed RIPK3's dual role in neuronal cell death, emphasizing its potential as a therapeutic target in neurodegenerative diseases (ref: Winkler doi.org/10.1016/j.immuni.2025.02.018/). Furthermore, Tai et al. characterized the interaction between the J-domain protein DNAJC12 and tyrosine hydroxylase, revealing how pathogenic variants can disrupt dopamine biosynthesis, a critical factor in PD (ref: Tai doi.org/10.1038/s41467-025-57733-6/). Zhu et al. investigated the NLRP3 inflammasome's role in PD, demonstrating that dephosphorylation at Serine 658 alleviates glial inflammation, which is pivotal in PD pathogenesis (ref: Zhu doi.org/10.1186/s13024-025-00818-z/). Sirerol-Piquer et al. examined age-dependent microglial responses to alpha-synuclein aggregates, highlighting how aging affects microglial function and contributes to PD pathology (ref: Sirerol-Piquer doi.org/10.1186/s13024-025-00816-1/). Together, these studies provide a comprehensive view of the cellular and molecular dynamics in PD, emphasizing the interplay between genetic factors, neuroinflammation, and cellular stress responses.

Neuroinflammation has emerged as a critical factor in neurodegenerative diseases, with recent studies highlighting its role in aging and disease progression. Kivimäki et al. demonstrated that social disadvantage accelerates aging, linking proteomic signatures of immune aging to increased risk of age-related diseases (ref: Kivimäki doi.org/10.1038/s41591-025-03563-4/). Omar et al. investigated endothelial TDP-43 depletion and its impact on the blood-brain barrier, revealing how neurodegeneration disrupts critical pathways in Alzheimer's disease and other disorders (ref: Omar doi.org/10.1038/s41593-025-01914-5/). Schneeberger et al. focused on interleukin-12 signaling, finding that it exacerbates AD pathology by disrupting neuronal and oligodendrocyte homeostasis, suggesting potential therapeutic targets in inflammatory pathways (ref: Schneeberger doi.org/10.1038/s43587-025-00816-2/). Koss et al. explored the relationship between genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies, indicating a reciprocal relationship that may inform future diagnostic and therapeutic strategies (ref: Koss doi.org/10.1186/s13024-025-00813-4/). Vrancx et al. highlighted the failure of lysosome repair in aging and AD, linking epigenetic changes to neurodegenerative processes (ref: Vrancx doi.org/10.1038/s41556-024-01608-3/). Collectively, these findings underscore the importance of neuroinflammation in the pathogenesis of neurodegenerative diseases, emphasizing the need for integrated approaches to address both inflammatory and neurodegenerative mechanisms.

The exploration of cognitive decline and biomarkers has gained momentum, particularly in the context of Alzheimer's disease and related disorders. Ossenkoppele et al. conducted a comprehensive study comparing plasma p-tau217 and tau-PET imaging, finding both biomarkers to be strong predictors of cognitive decline among cognitively unimpaired individuals, thus highlighting their potential utility in clinical trials (ref: Ossenkoppele doi.org/10.1038/s43587-025-00835-z/). Berlind et al. investigated excitotoxicity in tauopathy patient organoids, revealing that KCTD20 suppression mitigates neurodegeneration, suggesting a novel therapeutic avenue (ref: Berlind doi.org/10.1016/j.neuron.2025.02.001/). Moreover, Kim et al. examined the role of PARIS in Parkinson's disease, linking its transcriptional repression to mitochondrial dysfunction and neuron loss, which may also contribute to cognitive decline (ref: Kim doi.org/10.1186/s13024-025-00814-3/). Yang et al. introduced EnrichDO, a model for Disease Ontology enrichment analysis, which could enhance our understanding of gene-disease associations relevant to cognitive decline (ref: Yang doi.org/10.1093/gigascience/). These studies collectively emphasize the critical role of biomarkers in predicting cognitive decline and the potential for targeted interventions in neurodegenerative diseases.

Research into the molecular mechanisms underlying neurodegeneration has unveiled several critical pathways and regulatory processes. Zhou et al. identified the role of S-palmitoylation in regulating ferroptosis sensitivity through glutathione peroxidase 4 (GPX4), linking this process to neurodegenerative conditions (ref: Zhou doi.org/10.1038/s43018-025-00937-y/). Mangiarotti et al. explored how lipid packing and cholesterol content influence biomolecular condensates and membrane remodeling, shedding light on cellular processes relevant to neurodegeneration (ref: Mangiarotti doi.org/10.1038/s41467-025-57985-2/). Qi et al. utilized cryo-electron microscopy to investigate tau filaments in human MAPT mutants, revealing structural insights that could inform therapeutic strategies targeting tau aggregation (ref: Qi doi.org/10.1038/s41594-025-01498-5/). Green et al. focused on cryptic mitochondrial DNA mutations, demonstrating their accumulation in single cells and their potential pathophysiological relevance in aging and neurodegeneration (ref: Green doi.org/10.1038/s41467-025-57286-8/). Zhu et al. highlighted FTO's role in suppressing DNA repair by inhibiting PARP1, suggesting a novel regulatory mechanism in the DNA damage response (ref: Zhu doi.org/10.1038/s41467-025-58309-0/). These findings collectively enhance our understanding of the molecular underpinnings of neurodegeneration, paving the way for innovative therapeutic approaches.

Neuroprotective strategies have emerged as a focal point in the quest to mitigate neurodegenerative diseases. Coughlan et al. conducted a meta-analysis on sex differences in tau-PET imaging, revealing that female sex is associated with faster tau accumulation, which may inform tailored neuroprotective strategies (ref: Coughlan doi.org/10.1001/jamaneurol.2025.0013/). Ali et al. identified robust molecular signatures across the Alzheimer's disease continuum through cerebrospinal fluid proteomics, emphasizing the potential for these biomarkers to guide neuroprotective interventions (ref: Ali doi.org/10.1016/j.neuron.2025.02.014/). Chen et al. explored the impact of maternal behavior on resilience to stress in mice, linking early life experiences to neuroprotective mechanisms that could be harnessed in therapeutic contexts (ref: Chen doi.org/10.1038/s41467-025-57810-w/). Zhang et al. demonstrated functional optic tract rewiring through axonal regeneration and synaptic activity enhancement, providing insights into potential neuroprotective strategies following CNS injuries (ref: Zhang doi.org/10.1038/s41467-025-57445-x/). Govindarajan et al. utilized machine learning to identify neuroanatomical signatures of cardiovascular and metabolic diseases, which could inform neuroprotective strategies in at-risk populations (ref: Govindarajan doi.org/10.1038/s41467-025-57867-7/). These studies collectively highlight the importance of understanding neuroprotective mechanisms and developing targeted interventions to combat neurodegeneration.

Dietary patterns have been shown to significantly influence healthy aging, with recent studies emphasizing the importance of nutrition in promoting longevity and reducing disease risk. Tessier et al. identified optimal dietary patterns for healthy aging, noting that adherence to a healthful plant-based diet and the Alternative Healthy Eating Index was associated with increased odds of healthy aging (ref: Tessier doi.org/10.1038/s41591-025-03570-5/). This study highlights the potential of dietary interventions in enhancing quality of life as populations age. Kivimäki et al. further explored the relationship between social disadvantage and accelerated aging, linking specific age-related proteins to increased disease risk, which underscores the importance of addressing social determinants of health in dietary recommendations (ref: Kivimäki doi.org/10.1038/s41591-025-03563-4/). Rash et al. investigated the effects of allogeneic mesenchymal stem cell therapy in mild Alzheimer's disease, suggesting that dietary and lifestyle factors may interact with therapeutic strategies to influence disease progression (ref: Rash doi.org/10.1038/s41591-025-03559-0/). Together, these findings emphasize the critical role of diet in aging and neurodegeneration, advocating for integrated approaches that consider both nutritional and social factors in promoting healthy aging.