Recent studies have elucidated various genetic and molecular mechanisms contributing to Alzheimer's disease (AD). A significant advancement is the development of a polygenic risk score (PGS) derived from European ancestry populations, which has shown transferability across multi-ancestry populations, enhancing the prediction of AD risk when the APOE region is included (ref: Nicolas doi.org/10.1038/s41588-025-02227-w/). Another critical finding involves the R136S mutation in the APOE3 gene, which appears to confer resilience against tau pathology by inhibiting the cGAS-STING-IFN pathway, thereby reducing tau load and protecting against cognitive decline in carriers (ref: Naguib doi.org/10.1016/j.immuni.2025.05.023/). Additionally, the study of traumatic brain injury (TBI) has revealed injury-specific proteomic signatures that increase the risk of neurodegenerative diseases, including AD, highlighting the need for further investigation into the molecular alterations following TBI (ref: Mantash doi.org/10.1038/s41392-025-02286-9/). Moreover, the role of inflammation in AD progression has been underscored by findings that PSEN1 mutations lead to altered inflammatory responses in astrocytes, suggesting a link between genetic predisposition and neuroinflammatory processes (ref: Ziff doi.org/10.1186/s13024-025-00864-7/). The identification of myelin-axon interface vulnerabilities through subcellular proteomics has also provided insights into the structural disruptions occurring in AD, emphasizing the importance of myelin integrity for neuronal function (ref: Cai doi.org/10.1038/s41593-025-01973-8/).

The exploration of biomarkers for Alzheimer's disease (AD) has gained momentum, particularly in improving diagnostic accuracy and prognostic assessments. A longitudinal cohort study highlighted the potential of plasma biomarkers, specifically p-tau217 and GFAP, for predicting amyloid and tau brain deposition in individuals with Down syndrome, suggesting their utility in clinical and research settings (ref: Janelidze doi.org/10.1016/S1474-4422(25)00158-9/). Furthermore, a novel bioelectronic platform utilizing organic electrochemical transistors has demonstrated the ability to detect multiple blood extracellular vesicle biomarkers for AD, indicating a significant advancement in non-invasive diagnostic techniques (ref: Zheng doi.org/10.1002/adma.202505262/). In a multicenter study, plasma tau biomarkers were evaluated for their diagnostic performance in diverse populations, revealing that p-tau217 effectively classified Aβ-PET and tau-PET positivity, correlating with AD-related outcomes (ref: Lan doi.org/10.1038/s43587-025-00904-3/). Additionally, tau PET positivity was associated with a high risk of clinical progression to dementia, emphasizing the relevance of tau imaging in monitoring disease trajectory (ref: Moscoso doi.org/10.1001/jama.2025.7817/). These findings collectively underscore the critical role of biomarkers in enhancing the understanding and management of AD.

Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD), with recent studies highlighting the dual nature of immune responses in neurodegenerative processes. Research has shown that microglia can exert protective effects during tauopathy by regulating the spread of phosphorylated tau in the central nervous system, suggesting that innate immune responses may slow disease progression (ref: Mason doi.org/10.1038/s41590-025-02198-4/). Conversely, mutations in PSEN1 have been linked to altered inflammatory responses in astrocytes, indicating that genetic factors can exacerbate neuroinflammatory pathways and contribute to AD progression (ref: Ziff doi.org/10.1186/s13024-025-00864-7/). Moreover, the PKCι-β-arrestin2 axis has been identified as a mechanism that disrupts SORLA trafficking, leading to amyloid pathology, thus illustrating how immune signaling pathways can influence amyloidogenesis (ref: Rehman doi.org/10.1186/s13024-025-00865-6/). The interplay between neuroinflammation and amyloid deposition underscores the complexity of immune responses in AD, necessitating further exploration of therapeutic strategies targeting these pathways.

Cognitive decline in Alzheimer's disease (AD) is multifaceted, with recent studies elucidating various factors contributing to this deterioration. Research has demonstrated that white matter abnormalities, particularly in limbic tracts, are significantly associated with cognitive performance and decline, with free water in these tracts showing strong correlations with memory performance (ref: Peter doi.org/10.1001/jamaneurol.2025.1601/). Additionally, the presence of seizures in individuals with AD has been linked to accelerated cognitive decline, particularly affecting executive function and processing speed, highlighting the need for comprehensive management of comorbid conditions (ref: Reyes doi.org/10.1002/ana.27284/). Furthermore, the frequency of tau PET positivity has been associated with a high risk of progression to dementia, with a notable 70% absolute risk observed in individuals with MCI who also tested positive for Aβ (ref: Moscoso doi.org/10.1001/jama.2025.7817/). These findings emphasize the importance of early detection and intervention strategies to mitigate cognitive decline in AD patients.

The impact of lifestyle and environmental factors on the risk of Alzheimer's disease (AD) has garnered increasing attention. A study assessing the consumption of sweetened beverages found no significant association between the intake of sugar-sweetened and artificially sweetened beverages and the risk of all-cause dementia in older adults, suggesting that dietary factors may not play as critical a role as previously thought (ref: Chen doi.org/10.1001/jamapsychiatry.2025.1230/). In contrast, research on rural-urban living conditions revealed that individuals who lived in rural areas during childhood had a higher risk of mild cognitive impairment (MCI) and dementia, indicating that environmental factors throughout the lifespan can influence cognitive health (ref: Chu doi.org/10.1002/alz.70267/). Moreover, the role of myeloid-mediated cerebral amyloid vasculitis in brain atrophy has been highlighted, suggesting that immune responses may contribute to neurodegenerative processes following anti-amyloid therapy (ref: Castellani doi.org/10.1172/JCI195137/). These findings collectively underscore the complex interplay between lifestyle, environmental factors, and the risk of AD.

Innovative therapeutic strategies for Alzheimer's disease (AD) are being explored, particularly focusing on presymptomatic interventions and the potential of existing medications. One promising approach involves the use of semaglutide, a glucagon-like peptide-1 receptor agonist, which may offer neuroprotective benefits for individuals at high risk, such as APOE4 homozygotes (ref: Daly doi.org/10.1002/alz.70422/). This highlights the importance of targeting early stages of AD to slow disease progression. Additionally, the integration of digital biomarkers and artificial intelligence in AD research is gaining traction, with a scoping review revealing a significant number of studies and models aimed at improving diagnostic accuracy and monitoring disease progression (ref: Qi doi.org/10.1038/s41746-025-01640-z/). Moreover, the feasibility of using eye-tracking technology for cognitive screening in individuals with Down syndrome, who are at increased risk for dementia, has been investigated, suggesting a non-verbal method for assessing cognitive function (ref: Lindner doi.org/10.1002/alz.70385/). These advancements underscore the need for innovative approaches in the management and treatment of AD.

Neuroimaging and pathological studies are crucial for understanding the progression of Alzheimer's disease (AD) and identifying potential biomarkers. Recent findings indicate that plasma biomarkers, such as p-tau217, can predict amyloid and tau deposition in individuals with Down syndrome, enhancing prognostic assessments (ref: Janelidze doi.org/10.1016/S1474-4422(25)00158-9/). Additionally, tau PET imaging has been shown to correlate with clinical outcomes, with a significant risk of progression to dementia observed in individuals with tau PET positivity (ref: Moscoso doi.org/10.1001/jama.2025.7817/). Furthermore, studies on amygdalar and hippocampal volume loss in individuals with limbic-predominant age-related TDP-43 encephalopathy have revealed significant differences in brain structure associated with AD pathology, emphasizing the importance of neuroimaging in diagnosing and monitoring disease progression (ref: Wesseling doi.org/10.1093/brain/). These insights collectively highlight the value of neuroimaging and pathological studies in advancing our understanding of AD.

The intersection of Down syndrome (DS) and Alzheimer's disease (AD) presents unique challenges and opportunities for research and intervention. Individuals with DS are at an increased risk for developing AD, and recent studies have explored various diagnostic approaches to identify AD onset in this population. One study highlighted the potential of small extracellular vesicles from neuronal origin as biomarkers for tracking dementia progression in individuals with DS, suggesting a novel avenue for early detection (ref: Ledreux doi.org/10.1002/alz.70380/). Additionally, the feasibility of using eye-tracking technology for cognitive screening in adults with DS has been investigated, indicating that this method may provide a non-verbal approach to assessing cognitive function in this population (ref: Lindner doi.org/10.1002/alz.70385/). As life expectancy for individuals with DS continues to improve, the risk of developing DS-associated AD will rise, necessitating innovative strategies for monitoring and intervention (ref: McGlinchey doi.org/10.1002/alz.70388/). These findings underscore the importance of tailored approaches to address the unique needs of individuals with DS at risk for AD.