UK Dementia Research Institute

Protocol for genome-wide differential methylation using long-read DNA sequencing in the cortex of a mouse model of Alzheimer’s disease

Third-generation sequencing enables direct detection of genome-wide 5-methylcytosine without bisulfite conversion. Here, we present a protocol for generating long-read DNA sequencing from mouse cortex and performing genome-wide differential methylation analysis. We describe steps...

Combat Injury, Limb Loss, Traumatic Brain Injury, and Psychosocial Outcomes Among Military Personnel

Importance Given the burden and rising number of injuries from recent conflict zones such as Ukraine and the Middle East, understanding the long-term health outcomes of those with physical traumatic injuries is critical. Objective To investigate psychosocial outcomes among UK mil...

Hypokinesia and bradykinesia in Parkinson’s disease are consistent with reduced motor vigour, not an impaired capacity to generate and transmit neural drive to muscle

Abstract Hypokinesia and bradykinesia in Parkinson’s disease have been attributed to reduced motor vigour, an account that assumes the neural drive to muscle is intact but inappropriately scaled; an alternative is that generation of the drive is itself impaired. We recorded high-...

White matter dysfunction in Alzheimer’s disease: a convergence or divergence of hypotheses

Abstract Alzheimer’s disease (AD) is a multifactorial disease with several key hypotheses centred around its pathological hallmarks, including amyloid and tau and other mechanisms, such as vascular dysfunction. Revised criteria for AD diagnosis reflects these hypotheses and inclu...

Test-retest reliability of plasma biomarkers and digital cognitive metrics at clinically meaningful timescales

Abstract Background Digital cognitive testing and plasma biomarkers have emerged as key players for population screening and measuring drug efficacy in clinical trials for Alzheimer’s Disease (AD). Understanding test-retest reliability of these tools is essential to estimate mean...

Diagnosing autoimmune encephalitis in psychiatry: clinical recommendations and unresolved challenges from the GENERATE network

Psychiatric syndromes can be caused by underlying autoimmune encephalitis (AE). This represents a diagnostic challenge at the interface of psychiatry and neurology. While AE mostly manifests with a combined, complex neuropsychiatric syndrome, some patients with AE may (initially)...

Comparison of Actigraphy and Polysomnography in a Sleep Centre Cohort

ABSTRACT Polysomnography (PSG) is the gold standard for sleep assessment, but actigraphy offers a low‐cost, non‐invasive multi‐night alternative. MotionWatch 8 was compared to PSG in a tertiary sleep centre cohort ( n = 107; age 37.6 ± 14.9 years; 56% female), examining whether a...

Applying a systemic approach that extends beyond the brain to Alzheimer’s disease pathogenesis

Traditional dementia research often isolates single aspects, biomarkers or symptoms, overlooking complex interactions shaping disease risk and progression. Lysosomal and mitochondrial dysfunction, reflecting systemic processes, may explain links between Alzheimer’s and metabolic,...

Blood-based biomarkers of Alzheimer’s disease and neurodegeneration in an indigenous African cohort using both Simoa and NULISA platforms

Background: In low- and middle-income countries, Alzheimer's disease and related dementias (ADRD) constitute a growing public health burden. Indeed, the lack of awareness and easy screening tools, such as blood-based biomarkers, leaves many patients undiagnosed. In this study, we...

Activation of transposable elements is linked to a region- and cell type–specific interferon response in Parkinson’s disease

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder involving a neuroinflammatory response, the cause of which remains unclear. Transposable elements (TE) have been linked to inflammation, but their potential role in PD remains unexplored. Using bulk- and single-nuc...

Presymptomatic plasma biomarkers in autosomal dominant Alzheimer’s disease: sequence and timing

Abstract Background Autosomal dominant Alzheimer’s disease (ADAD) serves as a model for presymptomatic biomarker discovery. Characterising the temporal profile of plasma biomarker levels in presymptomatic individuals may enhance understanding of disease pathogenesis, inform futur...

Are different consumer sleep technologies measuring the same essential aspects of sleep?

Abstract Study objectives Consumer sleep technologies (CSTs) enable low-burden longitudinal sleep monitoring, and their output measures are often interpreted as equivalent to polysomnography (PSG) measures. We applied a measurement reliability-aware approach to determine whether...

The Association of Umbilical Cord Blood Neurofilament Light With Nonreassuring Fetal Status: A Prospective Observational Study

( Int J Gynaecol Obstet . 2026 Mar;172(3):1491–1500. doi:10.1002/ijgo.70421) A prospective observational study explored whether neurofilament light (NfL), a marker of neuronal injury, can be reliably measured in umbilical cord blood and whether it is associated with nonreassuring...

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures

We developed a high-content screening to investigate how Alzheimer’s disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently d...

Data-driven mapping of known and novel fluid biomarker progression profiles in genetic frontotemporal lobar degeneration

Abstract Introduction Recent proteomic studies have identified both established and novel proteins in genetic frontotemporal lobar degeneration (FTLD). However, it remains unclear at what point in the disease these proteins deviate from normal levels and how their trajectories re...

Serum Glial Fibrillary Acidic Protein Dynamics, Disease Progression, and Therapy Response in Multiple Sclerosis

Importance: Capturing individual multiple sclerosis (MS) progression is difficult; few studies have evaluated glial fibrillary acidic protein (GFAP) in large longitudinal cohorts with independent validation. Objective: To investigate whether serum GFAP levels and treatment-relate...