Journal Article

Heterozygous missense mutations in MORC2 have been implicated in various clinical entities, ranging from early-onset neurodevelopmental disorders to late-onset neuropathies. The mechanism underlying the phenotypic heterogeneity and pleiotropic effects of MORC2 has remained elusive. [...]

Tau species lacking truncation of the N-terminal region, including plasma N-terminal tau fragment 1 (NT1), have been previously associated with cognitive decline, neurodegeneration, and tau pathology in late-onset sporadic Alzheimer's disease (AD).Here, we examined cross-sectional and longitudinal plasma NT1 as a possible predictor of cognitive, clinical, and core AD biomarker trajectories in autosomal dominant AD (ADAD).NT1 levels in ADAD mutation carriers (MC; n = 132) increased across the disease continuum, compared to non-carriers (NC; n = 75), becoming elevated about a decade prior to estimated symptom onset. Cross-sectional and longitudinal NT1 levels in MC were associated with clinical, cognitive, and biomarker changes. [...]

There is substantial heterogeneity in clinical presentation of genetic Frontotemporal Dementia (FTD), even within the same family. This suggests that additional heritability may exist and contribute to this variable presentation. [...]

Aggregation of amyloid beta (Aβ) and tau proteins is a hallmark of Alzheimer's disease (AD) and tauopathies. In AD, extracellular deposition of Aβ peptide precedes tau aggregation and the onset of neuroinflammatory processes. [...]

Background: Understanding factors influencing Alzheimer's disease (AD) progression is crucial for optimising treatment timing and targets. A major genetic risk factor, the Apolipoprotein E ε4 allele (ApoE4), is associated with earlier tau pathology accumulation and spread at lower amyloid-beta (Aβ) levels (Steward, JAMA Neurol, 2023). [...]

Aging, a major risk factor for numerous diseases, is associated with significant transcriptional changes across organs. However, the age of onset, extent of transcriptomic changes and how they unfold are not fully understood. [...]

To comprehensively characterize complement pathway activation in chronic inflammatory demyelinating polyneuropathy (CIDP) and its association with clinical disease features using advanced complement profiling.Complement protein levels indicative of classical, lectin, and alternative pathway activation were quantified by multiplex ELISA and compared between 28 patients with typical CIDP, 24 patients with Charcot-Marie Tooth neuropathy (CMT), and 24 demographically matched healthy controls (HD).Serum levels of activated complement proteins-C3a, C4a, Ba, Bb, C5a, and the soluble terminal complement complex sC5b-9 (sTCC)-were significantly elevated in CIDP patients compared to healthy donors (HD) (p < 0.001). Except for C3a, these protein levels were also significantly higher in CIDP patients than in those with Charcot-Marie-Tooth disease (CMT). [...]

Severe optic neuritis (ON) is a common clinical manifestation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Given distinct prognoses and often the necessity of early plasma exchange in NMOSD, prompt differentiation is crucial. [...]

Down syndrome (DS) is a genetic cause of Alzheimer's disease (AD), with virtually all individuals developing AD pathology by their fourth decade due to Amyloid Precursor Protein (APP) gene overexpression. In addition to amyloid beta (Aβ) plaques and hyperphosphorylated tau (p-Tau) aggregates, DS-associated AD (DSAD) often includes α-synuclein (αSyn) aggregates, contributing to Lewy body pathology (LBP). [...]

Background:High-resolution (7T) MRI facilitates in vivo imaging of fine anatomical structures selectively affected in Alzheimer's disease (AD), including medial temporal lobe subregions. However, 7T data is challenging to acquire and largely unavailable in clinical settings. [...]