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Neuronal primary cilia, vital for signaling and cell-cycle regulation, have been implicated in maintaining neuronal identity. While a link between primary ciliary defects and neurodegenerative diseases is emer...
Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3–5 years of disease onset. Although roughly 10% of cases can be linked to a ...
The development of anti-amyloid-beta (Aβ) immunotherapies as the first disease modifying therapy for Alzheimer’s Disease (AD) is a breakthrough of basic research and translational science.
Tau protein plays a critical role in the physiological functioning of the central nervous system by providing structural integrity to the cytoskeletal architecture of neurons and glia through microtubule assem...
While APP is largely neuonally expressed, Aβ amyloid is largely produced by microglia as the clearance mechanisms for damaged membranes becomes overwhelmed.
Increased phosphorylation of TDP-43 is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the regulation a...
While the temporal profile of amyloid (Aβ) and tau cerebrospinal fluid (CSF) biomarkers along the Alzheimer’s disease (AD) continuum is well-studied, chronological changes of CSF proteins reflecting other dise...
Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms have not been extensively studied.
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with ...
In recent years, the seed amplification assay (SAA) has enabled the identification of pathological TDP-43 in the cerebrospinal fluid (CSF) and olfactory mucosa (OM) of patients with genetic forms of frontotemp...
Autosomal Dominant Alzheimer's Disease (ADAD), caused by mutations in Presenilins (PSEN1/2) and Amyloid Precursor Protein (APP) genes, typically manifests with early onset (< 65 years). Age at symptom onset (AAO)...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects the motor neurons, causing progressive muscle weakness and paralysis. While research has focused on understanding patho...
Apolipoprotein E (APOE- gene; apoE- protein) is the strongest genetic modulator of late-onset Alzheimer’s disease (AD), with its three major isoforms conferring risk for disease ε2 < ε3 < ε4. Emerging protective ...
Lewy body dementia (LBD) encompasses neurodegenerative dementias characterized by cognitive fluctuations, visual hallucinations, and parkinsonism. Clinical differentiation of LBD from Alzheimer’s disease (AD) ...
Genetic variation in Transmembrane protein 106B (TMEM106B) is known to influence the risk and presentation in several neurodegenerative diseases and modifies healthy aging. While evidence from human studies su...
The epoxyeicosatrienoic acids (EETs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by soluble epoxide hydr...
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor predominantly expressed by microglia in the brain. Recent studies have established TREM2 as a central immune signaling hub ...
There is currently no effective therapy for prion diseases. The glymphatic system is an organized system of perivascular spaces that facilitates the removal of metabolic waste from the brain. This study demons...
GPNMB has been discussed as a potential therapeutic target in GRN-mediated neurodegeneration, based on the observed reproducible upregulation in FTD-GRN cerebrospinal fluid (CSF) and post-mortem brain. However, t...
Immune mechanisms play a fundamental role in Alzheimer’s disease (AD) pathogenesis, suggesting that approaches which target immune cells and immunologically relevant molecules can offer therapeutic opportuniti...
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are overwhelmingly linked to TDP-43 dysfunction. Mutations in TDP-43 are rare, indicating that the progressive accumulation of exogenous fa...
Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play a central role. These immune cells undergo metabolic reprogramming in respons...
Parkinson’s disease (PD) is a multi-system disorder characterized histopathologically by degeneration of dopaminergic neurons in the substantia nigra pars compacta. While the etiology of PD remains multifactorial...
Alzheimer’s disease (AD) is the most common form of dementia globally and is characterised by reduced mitochondrial respiration and cortical deposition of amyloid-β plaques and neurofibrillary tangles comprise...
DNA damage and DNA damage repair (DDR) dysfunction are insults with broad implications for cellular physiology and have been implicated in various neurodegenerative diseases. Alpha-synuclein (aSyn), a pre-syna...
Aggregated alpha-Synuclein (αSyn) is a hallmark pathology in Parkinson’s disease but also one of the most common co-pathologies in Alzheimer’s disease (AD). Preclinical studies suggest that αSyn can exacerbate...
Alzheimer’s disease (AD) is neuropathologically characterized by the extracellular deposition of the amyloid-β peptide (Aβ) and the intraneuronal accumulation of abnormal phosphorylated tau (τ)-protein (p-τ). ...
Tauopathies represent a diverse group of neurodegenerative disorders characterized by the abnormal aggregation of the microtubule-associated protein tau. Despite extensive research, the mechanisms underlying t...
Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic...
Recent studies highlight the critical role of microglia in neurodegenerative disorders, and emphasize the need for humanized models to accurately study microglial responses. Human-mouse microglia xenotransplan...
Axon regeneration within the mammalian central nervous system is extremely limited. In optic neuropathy conditions like glaucoma, the inability of retinal ganglion cell (RGC) axons to regenerate is a major imp...
Parkinson’s disease (PD) is a leading neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, contributing to considerable disability worldwide. Current treatments offer only ...
Cytoplasmic alpha-synuclein (αSyn) aggregates are a typical feature of Parkinson’s disease (PD). Extracellular insoluble αSyn can induce pathology in healthy neurons suggesting that PD neurodegeneration may sp...
The relationship between Alzheimer's disease (AD) and neuroimmunity has gradually begun to be unveiled. Emerging evidence indicates that cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, recognizi...
The parkin-interacting substrate (PARIS, also known as ZNF746) is a transcriptional repressor, whose accumulation and phosphorylation play central pathological roles in Parkinson’s disease (PD). PARIS-induced ...
Molecular biomarkers of chronic traumatic encephalopathy (CTE) are lacking. We evaluated 18F-MK-6240 tau PET as a biomarker for CTE. Two studies were done: (1) 3H-MK-6240 autoradiography and an in-vitro brain hom...
Alzheimer’s disease (AD) poses a growing global health challenge as populations age. Recent research highlights the crucial role of peripheral immunity in AD pathogenesis. This review explores how blood-brain ...
Normal aging alters brain functions and phenotypes. However, it is not well understood how astrocytes are impacted by aging, nor how they contribute to neuronal dysfunction and disease risk as organisms age. H...
The integrated stress response (ISR) is a conserved network in eukaryotic cells that mediates adaptive responses to diverse stressors. The ISR pathway ensures cell survival and homeostasis by regulating protei...
Parkinson disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy are synucleinopathies, characterized by neuronal loss, gliosis and the abnormal deposition of α-synuclein in vulnerable areas...
Axon regeneration after injury to the central nervous system (CNS) is limited by an inhibitory environment but also because injured neurons fail to initiate expression of regeneration associated genes (RAGs). ...
Cortical atrophy is a common manifestation in behavioral variant frontotemporal degeneration (bvFTD), exhibiting spatial heterogeneity across various genetic subgroups, which may be driven by distinct biologic...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigene...
Cellular senescence, a hallmark of aging, has been implicated in Alzheimer’s disease (AD) pathogenesis. Cholesterol accumulation is known to drive cellular senescence; however, its underlying mechanisms are no...
Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the pos...
Many diseases and disorders of the nervous system suffer from a lack of adequate therapeutics to halt or slow disease progression, and to this day, no cure exists for any of the fatal neurodegenerative disease...
Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances in ...
Alzheimer’s disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to the involvement of lipid dysregulation in the development of AD. N...
α-Synucleinopathies constitute a spectrum of neurodegenerative disorders, including Parkinson’s disease (PD), Lewy body dementia (LBD), Multiple System Atrophy (MSA), and Alzheimer’s disease concurrent with LB...
Molecular Neurodegeneration