Molecular Neurodegeneration - Alpha-synucleinopathies are common disorders that are expected to become increasingly prevalent in the future along with the longer life expectancy. However, their...

Peripheral nerves have an intrinsic capacity for regeneration after traumatic injury, with Schwann cells (SCs) playing a central role in orchestrating this complex process. Critical components of succ...

Molecular Neurodegeneration - Protein truncating variants (PTVs) in SORL1 are observed almost exclusively in Alzheimer’s Disease (AD) cases, but the effect of rare SORL1 missense variants is...

Molecular Neurodegeneration - Alzheimer’s disease (AD) leading to cognitive decline and dementia results from the interplay of multiple interacting dysfunctional biological systems. These...

Novel plasma assays enabled accurate blood-based biomarkers for neurodegenerative diseases with minimally invasive options for clinical use. Large-scale studies encompassing multiple neurodegenerative...

M102 is a central nervous system (CNS) penetrant small molecule electrophile which activates in vivo the NF-E2 p45-related factor 2-antioxidant response element (NRF2-ARE) pathway, as well as transcri...

Lewy body dementia is the second most common form of neurodegenerative dementia, following Alzheimer’s disease. This umbrella term encompasses dementia with Lewy bodies (DLB) and Parkinson’s disease d...

Various plasma phosphorylated tau species have been shown to be associated with amyloid-β (Aβ) PET and Tau PET in Alzheimer’s disease (AD), but whether APOE ε4 affects the interaction between glial fi...

Microglia are the resident immune cell of the brain, and alterations in microglia signaling have been implicated in many neurodegenerative disorders. While microglia responses to central cues and othe...

Background The accumulation and propagation of α-synuclein (α-syn) are hallmark features of Parkinson’s disease (PD) and related neurodegenerative disorders. O-GlcNAcylation, an abundant post-translat...

The potential neuroprotective effects of antidiabetic treatments have been largely assessed in Alzheimer’s disease (AD) and AD-like dementia models, with or without metabolic disorders. In this Line, ...

With the disease modifying therapy Qalsody (tofersen) which targets the RNA product of the SOD1 gene, having been shown effective in amyotrophic lateral sclerosis (ALS), the present perspective seeks ...

Background Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease characterized by motor impairment resulting from the degeneration of dopaminergic neurons in the substantia n...

Background Synaptic homeostasis, maintained by microglia and astroglia, is disrupted throughout aging and early on in neurodegenerative diseases. Our aim was to study the relationship between TREM2-de...

Advertisement

Somatic mutations are DNA sequence changes that occur in non-reproductive cells during an organism’s life and are not inherited by offspring. Growing evidence implicates somatic mutations in Alzheimer’s disease (AD), linking them to both disease onset and progression. Recent advancements in single-cell sequencing and genome-wide analyses have revealed higher mutation burdens in neurons, particularly in AD-related genes such as Presenilin 1 (PSEN1), Presenilin 2 (PSEN2) and amyloid precursor protein (APP). These mutations, which include single nucleotide variants (SNVs), small insertions and deletions (Indels), structural variations (SVs) and mitochondrial DNA (mtDNA) mutations may disrupt neuronal function and synaptic connectivity. However, some somatic mutations may also serve a neuroprotective role. The underlying mechanisms remain incompletely understood. This review explores the emerging role of somatic mutations in AD, highlighting their links to disease progression. It also underscores the potential for future research to uncover new therapeutic targets by integrating advanced sequencing technologies and gene-editing approaches, which may enable more precise interventions to correct somatic mutations and slow disease progression.