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Amyotrophic lateral sclerosis (ALS) is caused by upper and lower motor neuron loss and has a fairly rapid disease progression, leading to fatality in an average of 2-5 years after symptom onset. Numerous genes...
Alzheimer’s disease (AD) is neuropathologically characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The main protein components of these hallmarks include Aβ40, Aβ42, tau, phosphor-tau, and...
We analyzed 35 population-based Mayo Clinic Study of Aging participants with plasma p-...
Cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) disease spectrum, causing both nuclea...
Abnormal lipid accumulation has been recognized as a key element of immune dysregulation in microglia whose dysfunction contributes to neurodegenerative diseases. Microglia play essential roles in the clearanc...
Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and its prevalence is rapidly increasing due to extended lifespans. Among the increasing number of genetic risk factors identified, the ...
The aggregation and spread of α-synuclein (α-Syn) protein and related neuronal toxicity are the key pathological features of Parkinson’s disease (PD) and Lewy body dementia (LBD). Studies have shown that patho...
Microglia, the resident immune cells of the brain, play a critical role in numerous diseases, but are a minority cell type and difficult to genetically manipulate in vivo with viral vectors and other approache...
Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address...
Epidemiological studies suggest a link between the melanoma-related pigmentation gene melanocortin 1 receptor (MC1R) and risk of Parkinson’s disease (PD). We previously showed that MC1R signaling can facilitate n...
Transactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear protein encoded by the TARDBP gene that is involved in RNA splicing, trafficking, stabilization, and thus, the regulation of gene exp...
Synucleinopathies are clinically and pathologically heterogeneous disorders characterized by pathologic aggregates of α-synuclein in neurons and glia, in the form of Lewy bodies, Lewy neurites, neuronal cytopl...
A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the ...
Parkinson’s disease is a disabling neurodegenerative movement disorder characterized by dopaminergic neuron loss induced by α-synuclein oligomers. There is an urgent need for disease-modifying therapies for Pa...
Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer’s disease (AD). Changes in the mitochondrial DNA copy number (mtDNAcn) and increased mitochondrial DNA mutation burden ...
Microtubule-associated protein tau is abnormally aggregated in neuronal and glial cells in a range of neurodegenerative diseases that are collectively referred to as tauopathies. Multiple studies have suggeste...
Human tauopathies including Alzheimer’s disease (AD) are characterized by alterations in the post-translational modification (PTM) pattern of Tau, which parallel the formation of insoluble Tau aggregates, neur...
Passive immunotherapies targeting Aβ continue to be evaluated as Alzheimer’s disease (AD) therapeutics, but there remains debate over the mechanisms by which these immunotherapies work. Besides the amount of p...
An amendment to this paper has been published and can be accessed via the original article.
The original article was published in Molecular Neurodegeneration 2021 16:18
Recent studies suggest that microglia contribute to tau pathology progression in Alzheimer’s disease. Amyloid plaque accumulation transforms microglia, the primary innate immune cells in the brain, into neurod...
The Correction to this article has been published in Molecular Neurodegeneration 2021 16:24
The most common mutation in the Leucine-rich repeat kinase 2 gene (LRRK2), G2019S, causes familial Parkinson’s Disease (PD) and renders the encoded protein kinase hyperactive. While targeting LRRK2 activity is...
Genome-wide association studies have established clusterin (CLU) as a genetic modifier for late-onset Alzheimer’s disease (AD). Both protective and risk alleles have been identified which may be associated wit...
Accumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark of Alzheimer’s disease (AD). The clusterin (CLU) gene confers a risk for AD and CLU is highly upregulated in AD patients, with the co...
Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer’s have focused on rare familial mutations, due to a lack of frank neuropathology from mo...
Investigations of apolipoprotein E (APOE) gene, the major genetic risk modifier for Alzheimer’s disease (AD), have yielded significant insights into the pathogenic mechanism. Among the three common coding variant...
An amendment to this paper has been published and can be accessed via the original article.
The original article was published in Molecular Neurodegeneration 2020 15:38
Large-scale brain bulk-RNAseq studies identified molecular pathways implicated in Alzheimer’s disease (AD), however these findings can be confounded by cellular composition changes in bulk-tissue. To identify ...
The Correction to this article has been published in Molecular Neurodegeneration 2020 15:54
An amendment to this paper has been published and can be accessed via the original article.
The original article was published in Molecular Neurodegeneration 2020 15:34
Ever since a GGGGCC hexanucleotide repeat expansion mutation in C9ORF72 was identified as the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), three competing b...
The Correction to this article has been published in Molecular Neurodegeneration 2020 15:37
Frontotemporal lobar degeneration (FTLD) is a devastating and progressive disorder, and a common cause of early onset dementia. Progranulin (PGRN) haploinsufficiency due to autosomal dominant mutations in the ...
The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. Th...
All samples were obtained through the ALS Center at Mayo Clinic Florida. Our primary cohort included 75 unrelated...C9orf72 repeat, 33 patients who did not possess this expansion, and 20 control subjects without ...
Misfolding and aggregation of the presynaptic protein alpha-synuclein (αsyn) is a hallmark of Parkinson’s disease (PD) and related synucleinopathies. Although predominantly localized in the cytosol, a body of ...
New genetic and genomic resources have identified multiple genetic risk factors for late-onset Alzheimer’s disease (LOAD) and characterized this common dementia at the molecular level. Experimental studies in ...
This article is part of a Supplement: Volume 14 Supplement 1
Alzheimer’s disease is a progressive neurodegenerative disease most often associated with memory deficits and cognitive decline, although less common clinical presentations are increasingly recognized. The car...
Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) TREM2 protein levels are different between AD cases and controls. Similarly, TREM2 risk variant...
A G4C2 hexanucleotide repeat expansion in the noncoding region of C9orf72 is the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). Putative disease mechanisms underlyin...
Activation of microglia, the resident immune cells of the central nervous system, is a prominent pathological hallmark of Alzheimer’s disease (AD). However, the gene expression changes underlying microglia act...
Rare coding variants ABI3_rs616338-T and PLCG2_rs72824905-G were identified as risk or protective factors, respectively, for Alzheimer’s disease (AD).
Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like the C9orf72 ‘GGGGCC’ (G4C2) repeat that causes approximately 5–7% of all amyotrophic lateral sclerosis (ALS) a...
Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is larg...
Single nucleotide polymorphisms (SNPs) inherited as one of two common haplotypes at the transmembrane protein 106B (TMEM106B) locus are associated with the risk of multiple neurodegenerative diseases, including f...
Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function...
Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer’s disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ...
Molecular Neurodegeneration