Journals
2026 EN
DuBois Makenna · Dixon Katherine · SherlawSturrock Charlotte
+10 more
The cover image is based on the article Identification of a Non‐Coding Causative Variant Underlying Warsaw Breakage Syndrome Using Long‐Read Based Genomic Sequencing and Transcriptome Analysis by Makenna DuBois et al., https://doi.org/10.1002/ajmg.a.64252 .
Journals
2026 EN
Stewart Rebecca · FitzGibbon Kate · Roberts Steven
ABSTRACT Australian policy and practice increasingly acknowledges the need to respond to children as victim‐survivors of domestic and family violence (DFV) in their own right. As part of this, and in recognition that schools often have the most consistent contact with young people experiencing DFV, there is mounting recognition of the role education settings can play in terms of early intervention and support provision for young victim‐survivors. However, there is little research on intervention and support provision in Australian education settings that draws directly on the experiences of young people who have experienced DFV. This article addresses that gap. Drawing on findings from a national survey of 1651 young people who reported experiences of DFV, this article enhances current understandings of how DFV impacts education and the effectiveness of school‐based help‐seeking for young Australians experiencing DFV. Centring the voices of young victim‐survivors, our findings question the degree to which schools are presently equipped to recognise, respond to and support students who experience DFV.
Journals
2026 EN
Rudd Bonnie · Roche Steven · Wagstaff Ruth
ABSTRACT Transitions from youth detention are central to short‐ and long‐term well‐being and recidivism outcomes for young people. This study aimed to map the extent of empirical research regarding young people's needs, experiences and influential factors when transitioning from Australian youth detention. A scoping review, conducted following Joanna Briggs Institute methodology, retrieved 540 documents and identified 14 studies from 1990 onward that met inclusion criteria. Qualitative studies ( n = 7) primarily highlighted the importance of external factors such as community, interpersonal and institutional conditions. Quantitative studies ( n = 7) mainly focused on individual factors, such as knowledge, lifetime substance use and psychiatric treatment. There were no transition interventions that tested post‐transition outcomes for young people in Australia. The study found preliminary evidence of the importance of reliable positive human connection in program staff, caseworkers and mentors and the importance of community awareness and interagency coordination. However, it also highlighted an absence of mixed‐methods studies or intervention outcome testing, which would be crucial to determining the common factors of successful transition programs. Future primary research to fill the gaps highlighted by this review is essential to ensure transition processes are meeting the needs of young people and the broader Australian community.
Journals
2026 EN
Callander Jacquelyn K. · Charbit Annabelle R. · Marshall Camryn
+7 more
Key Points Eosinophil peroxidase (EPX) correlates with local type 2 inflammation and may serve as a noninvasive biomarker of eosinophilic chronic rhinosinusitis. EPX declines after surgery and dupilumab, highlighting its potential to track treatment response. High baseline EPX predicts patients likely to achieve a clinically meaningful Sinonasal Outcome Test‐22 change.
Journals
2026 EN
Yaskolka Meir Anat · Wang Xingyan · Tasaki Shinya
+8 more
Abstract BACKGROUND Although considerable research has investigated diabetes mellitus (DM) as a risk factor for Alzheimer's disease (AD) dementia, the mechanistic understanding of the associations between peripheral and central biological processes in AD and AD within DM remains limited. METHODS We performed tandem mass tag‐based phosphoproteome profiling on postmortem prefrontal cortex ( n = 191), deltoid muscle ( n = 191), and antemortem serum ( n = 96) from older adults with/without pathologic AD and with/without DM (DM/NDM). RESULTS We observed significant brain–muscle and brain–serum correlations in phosphorylated and unphosphorylated peptides. Among individuals with DM, 59 were with AD and 36 were without. Among NDM, 63 were with AD and 33 were without. In a differential expression analysis, muscle phosphorylated seryl‐tRNA synthetase 2 (SARS2)‐S126 was significantly expressed in pathologic AD, whereas relative abundance of serum alpha‐2‐HS‐glycoprotein (AHSG)‐S346 and insulin‐like growth factor binding protein 2 (IGFBP2)‐S142 showed marginal expression for AD within the DM strata. CONCLUSIONS Elucidating central and peripheral proteome crosstalk is valuable for uncovering potential AD biomarkers in accessible (peripheral) biospecimens. Highlights We profiled peptides in brain, muscle, and serum biosamples. The study design allowed discovery of diabetes‐associated peptides in Alzheimer's disease (AD). Strong brain–muscle, but weaker brain–serum peptide correlations were identified. Muscle seryl‐tRNA synthetase 2‐S126 was linked to AD pathology. Serum insulin‐like growth factor binding protein 2‐S142 and alpha‐2‐HS‐glycoprotein‐S346 were linked to AD in persons with diabetes.
Journals
2026 EN
Layden Rachael M. · Groh Jenna R. · Miner Annalise E.
+19 more
Abstract INTRODUCTION This studyexamined the independent contribution of chronic traumatic encephalopathy (CTE) neuropathology to symptoms. METHODS The sample included 614 brain donors with ( n = 366) and without ( n = 248) autopsy‐confirmed CTE. Brain donors with other major neurodegenerative disease diagnoses were excluded. Informants completed cognitive and neuropsychiatric measures. Dementia was determined during diagnostic consensus conferences. RESULTS CTE stage IV (of IV) was associated with 4.48 (95% confidence interval [CI] = 1.97–10.90) increased odds of having dementia. CTE stage III had an odds ratio of 2.12 (95% CI = 1.91–3.77). Higher CTE stage was associated with greater informant‐reported cognitive symptoms ( p < 0.01). There were no associations with mood/behavioral scales. DISCUSSION CTE stage III/IV neuropathology was associated with dementia and cognitive symptoms: those with stage IV were 4.5 times more likely to have dementia than those without CTE. It is uncertain if low‐stage CTE clinically manifests, and mood/behavioral symptoms likely have multifactorial causes and/or a fluctuating course. Highlights Stage III and IV chronic traumatic encephalopathy (CTE) are independently associated with increased odds of having dementia. Higher CTE stage was associated with greater informant‐reported cognitive symptoms. Stage I and II CTE were not associated with cognitive symptoms or dementia. CTE of any severity was not associated with informant‐reported mood or behavioral symptoms.
Journals
2026 EN
Piotrowski Stacey L. · Allnutt Mary Alice · Johnson Kory
+20 more
Abstract INTRODUCTION The infectious hypothesis suggests that microbes like herpesviruses may play a role in the pathogenesis of Alzheimer's disease (AD) and other related dementias through methods that may include viral genome integration. The occurrence of herpesvirus genome integration in dementia patients has not been thoroughly characterized. METHODS Over 7500 total whole‐genome sequences from control, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), multiple system atrophy (MSA), and AD cohorts were screened for the integration of pathogen genomes using the PathSeq computational tool. RESULTS Low PathSeq scores for human herpesvirus 6 (HHV‐6) were consistent with the suspected integration of viral genome segments. The LBD and MSA cohorts had a significantly higher prevalence of this partial HHV‐6 genome integration. DISCUSSION This higher prevalence in both synucleinopathies was not noted in other herpesviruses, suggesting that the integration of HHV‐6 may play a role in a subset of these patients. Highlights Over 7500 whole‐genome sequences from controls and dementia patients were analyzed. Sequences consistent with integrated herpesviruses were identified using PathSeq. Prevalence of partial HHV‐6 integration was higher in synucleinopathies. Herpesviruses genome integration may play a role in subsets of dementia patients.
Journals
2026 EN
Pentchev Julian V. · Jackson Trever · Khan Naazneen
+53 more
Abstract INTRODUCTION The genetic basis of sporadic early‐onset Alzheimer's disease (EOAD) remains largely unknown, prompting evaluation of late‐onset Alzheimer's disease (LOAD) polygenic risk in EOAD. METHODS A LOAD polygenic score (PGS) was calculated in the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) study and tested for associations with AD risk, cognitive performance, and imaging and fluid biomarkers. RESULTS Though PGS was elevated in LOAD and EOAD, it was not a significant predictor of EOAD adjusting for APOE ε4 carrier status and was not associated with age of EOAD onset ( p = 0.106) or with cognitive performance ( p = 0.417). In LEADS, greater LOAD PGS was associated with differences in neuroimaging and fluid biomarkers, including elevated synaptosomal‐associated protein 25 (SNAP‐25) ( p = 2.3 × 10 −5 ). DISCUSSION While LOAD polygenic risk contributed minimally to EOAD onset and cognitive dysfunction, PGS association with fluid biomarkers in LEADS suggests a role for LOAD polygenic risk in EOAD pathophysiology. Highlights LOAD PGSs were elevated in both LOAD and EOAD compared to controls; however, LOAD PGS did not significantly predict EOAD risk, age at onset, or cognitive performance independent of APOE ε4 in the LEADS. Higher LOAD PGS was associated with lower amyloid PET Centiloids (less brain amyloid deposition) as well as lower CSF biomarker Aβ42 in LEADS (proxy marker suggesting higher brain amyloid deposition) in LEADS; these contradictory findings support the need for larger studies to further investigate whether LOAD PGS is associated with increased amyloid deposition in EOAD. Higher LOAD PGS was also associated with higher levels of CSF synaptosomal‐associated protein 25 (SNAP‐25), a key component of the SNARE complex, suggesting that LOAD genetic factors may contribute to dysregulation of synaptic transmission and/or pathological protein aggregation in EOAD.
Journals
2026 EN
Chen Charles D. · Aguero Cinthya · Melloni Alexandra
+17 more
Abstract INTRODUCTION Alzheimer's disease (AD) biomarkers are assessed on their ability to detect AD pathophysiology in vivo, with confirmation of AD neuropathology only at autopsy. METHODS Positron emission tomography (PET), plasma, and cognitive AD biomarkers were compared to AD neuropathology in Harvard Aging Brain Study participants (10 cognitively unimpaired; 6 mild cognitive impairment). Different PET methods were evaluated, for example, standardized uptake volume ratio (SUVR), distribution volume ratio (DVR), spatial extent (EXT), and partial‐volume correction (PVC). RESULTS Amyloid beta (Aβ)–PET ( 11 C‐Pittsburgh compound B [PiB]), tau‐PET ( 18 F‐flortaucipir [FTP]), and plasma tau phosphorylated at threonine 217 (p‐tau217) correlate with Aβ plaques (A‐score), Braak tau neurofibrillary tangle (NFT) stage (B‐score), and neuritic plaques (C‐score), whereas plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and cognitive measures did not; although digital Clock Drawing Test (dCDT) latency features did, in an exploratory comparison. Correlations were stronger for Aβ‐PET DVR and Aβ‐PET EXT (than SUVR with/without PVC) and tau‐PET SUVR (composite reference and PVC). DISCUSSION These findings support the innovative use of imaging, plasma, and digital cognitive tools for detecting AD pathophysiology in a largely cognitively unimpaired population. Highlights Amyloid beta–positron emission tomography (Aβ‐PET), tau‐PET imaging, and plasma tau phosphorylated at threonine 217 (p‐tau217) correlate with ABC scores Correlations were larger for Aβ‐PET distribution volume ratio (DVR) and tau‐PET standardized uptake volume ratio (SUVR; composite reference, partial volume correction [PVC]) Digital Clock Drawing Test latency features correlate with A‐ and Cscores Standard cognitive measures mostly did not correlate with ABC scores Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) biomarkers did not correlate with ABC scores
Journals
2026 EN
Peyton Madeline · JuryGarfe Nur · Liu Jiahui
+10 more
Abstract INTRODUCTION Alzheimer's disease (AD) involves β‐amyloid (Aβ) accumulation, tau pathology, and neuroinflammation, driving cognitive decline. Despite extensive research, disease‐modifying therapies remain elusive. We integrated single‐cell RNA sequencing (scRNA‐seq), spatial transcriptomics, and in vitro validation to identify repurposable drugs for AD 1 . METHODS Computational drug repurposing was performed using cell‐type‐specific analysis of scRNA‐seq datasets from AD cortical regions. Trichostatin‐A (TSA) effects were validated in human induced pluripotent stem cells (iPSC) ‐derived cortical neurons exposed to Aβ oligomers. Cross‐dataset integration identified convergent therapeutic targets. RESULTS TSA emerged as the top candidate, protecting neurons from Aβ toxicity and preserving synaptic integrity. DISC1 (Disrupted‐In‐Schizophrenia 1) was uniquely upregulated across TSA‐treated neurons, AD‐associated neuronal subpopulations, and protective microglial subtypes. DISCUSSION DISC1 represents a convergent therapeutic target for AD, mediating TSA's neuroprotective effects through pathways regulating GSK3β , mitochondrial transport, and synaptic plasticity, providing a mechanistic framework for developing AD therapeutics.