Judith Stefanie Schlett, Melanie Mettang, Aladdin Skaf, Pavel Schweizer, Alina Errerd, Ephraim Alemayehu Mulugeta, Tabea Melissa Hein, Konstantinos Tsesmelis, Miltiadis Tsesmelis, Ulrike F G Büttner, Heinrich Wendt, Alireza Abaei, Volker Rasche, Vivien Prex, Ester Nespoli, Najwa Ouali Alami, Daniel Tews, Paul Walther, Deniz Yilmazer-Hanke, Franz Oswald, Leda Dimou, Thomas Wirth, Bernd Baumann
BACKGROUND: Inflammaging represents an accepted concept where the immune system shifts to a low-grade chronic pro-inflammatory state without overt infection upon aging. In the CNS, inflammaging is mainly driven by glia cells and associated with neurodegenerative processes. White matter degeneration (WMD), a well-known process in the aging brain, manifests in myelin loss finally resulting in motor, sensory and cognitive impairments. Oligodendrocytes (OL) are responsible for homeostasis and maintenance of the myelin sheaths, which is a complex and highly energy demanding process sensitizing these cells to metabolic, oxidative and other forms of stress...
April 17, 2023: Molecular Neurodegeneration
Dongqin Wu, Nana Yu, Yang Gao, Rui Xiong, Luping Liu, Huiyang Lei, Sen Jin, Jiale Liu, Yingzhou Liu, Jiazhao Xie, Enjie Liu, Qiuzhi Zhou, Yanchao Liu, Shihong Li, Linyu Wei, Jingru Lv, Huilin Yu, Wenbo Zeng, Qiang Zhou, Fuqiang Xu, Min-Hua Luo, Yao Zhang, Ying Yang, Jian-Zhi Wang
BACKGROUND: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer's disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. METHODS: To investigate the effect and mechanism of the cholinergic circuit in Alzheimer's disease-related hippocampal memory, overexpression of human wild-type Tau (hTau) in medial septum (MS)-hippocampus (HP) cholinergic was achieved by specifically injecting pAAV-EF1α-DIO-hTau-eGFP virus into the MS of ChAT-Cre mice...
April 14, 2023: Molecular Neurodegeneration
Nimansha Jain, David M Holtzman
No abstract text is available yet for this article.
April 5, 2023: Molecular Neurodegeneration
Yan Yan, Casey N Cook
No abstract text is available yet for this article.
April 5, 2023: Molecular Neurodegeneration
Giovanni Bellomo, Silvia Paciotti, Luis Concha-Marambio, Domenico Rizzo, Anna Lidia Wojdaƚa, Davide Chiasserini, Leonardo Gatticchi, Linda Cerofolini, Stefano Giuntini, Chiara Maria Giulia De Luca, Yihua Ma, Carly M Farris, Giuseppe Pieraccini, Sara Bologna, Marta Filidei, Enrico Ravera, Moreno Lelli, Fabio Moda, Marco Fragai, Lucilla Parnetti, Claudio Luchinat
BACKGROUND: Aggregation of α-synuclein (α-syn) is a prominent feature of Parkinson's disease (PD) and other synucleinopathies. Currently, α-syn seed amplification assays (SAAs) using cerebrospinal fluid (CSF) represent the most promising diagnostic tools for synucleinopathies. However, CSF itself contains several compounds that can modulate the aggregation of α-syn in a patient-dependent manner, potentially undermining unoptimized α-syn SAAs and preventing seed quantification...
April 1, 2023: Molecular Neurodegeneration
Julia Tcw, Amaia M Arranz
No abstract text is available yet for this article.
March 25, 2023: Molecular Neurodegeneration
Fernando Gonzalez-Ortiz, Przemysław R Kac, Wagner S Brum, Henrik Zetterberg, Kaj Blennow, Thomas K Karikari
As the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, and healthcare systems. Although AD can be identified and diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence and clinical symptoms, challenges regarding practicality and accessibility hinder their widespread availability and implementation. Consequently, many people with suspected cognitive impairment due to AD do not receive a biomarker-supported diagnosis...
March 16, 2023: Molecular Neurodegeneration
Monica Xiong, Chao Wang, Maud Gratuze, Fareeha Saadi, Xin Bao, Megan E Bosch, Choonghee Lee, Hong Jiang, Javier Remolina Serrano, Ernesto R Gonzales, Michal Kipnis, David M Holtzman
BACKGROUND: Alzheimer Disease (AD) and cerebral amyloid angiopathy (CAA) are both characterized by amyloid-β (Aβ) accumulation in the brain, although Aβ deposits mostly in the brain parenchyma in AD and in the cerebrovasculature in CAA. The presence of CAA can exacerbate clinical outcomes of AD patients by promoting spontaneous intracerebral hemorrhage and ischemia leading to CAA-associated cognitive decline. Genetically, AD and CAA share the ε4 allele of the apolipoprotein E (APOE) gene as the strongest genetic risk factor...
March 16, 2023: Molecular Neurodegeneration
Puja R Mehta, Anna-Leigh Brown, Michael E Ward, Pietro Fratta
TDP-43 is an RNA-binding protein with a crucial nuclear role in splicing, and mislocalises from the nucleus to the cytoplasm in a range of neurodegenerative disorders. TDP-43 proteinopathy spans a spectrum of incurable, heterogeneous, and increasingly prevalent neurodegenerative diseases, including the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum and a significant fraction of Alzheimer's disease. There are currently no directed disease-modifying therapies for TDP-43 proteinopathies, and no way to distinguish who is affected before death...
March 15, 2023: Molecular Neurodegeneration
Vyara Todorova, Mia Fee Stauffacher, Luca Ravotto, Sarah Nötzli, Duygu Karademir, Lynn J A Ebner, Cornelia Imsand, Luca Merolla, Stefanie M Hauck, Marijana Samardzija, Aiman S Saab, L Felipe Barros, Bruno Weber, Christian Grimm
BACKGROUND: Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR. METHODS: We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells...
March 7, 2023: Molecular Neurodegeneration
Kassandra Kisler, Abhay P Sagare, Divna Lazic, Sam Bazzi, Erica Lawson, Ching-Ju Hsu, Yaoming Wang, Anita Ramanathan, Amy R Nelson, Zhen Zhao, Berislav V Zlokovic
No abstract text is available yet for this article.
February 24, 2023: Molecular Neurodegeneration
Stephan A Müller, Merav D Shmueli, Xiao Feng, Johanna Tüshaus, Neele Schumacher, Ryan Clark, Brad E Smith, An Chi, Stefan Rose-John, Matthew E Kennedy, Stefan F Lichtenthaler
BACKGROUND: The protease BACE1 is a major drug target for Alzheimer's disease, but chronic BACE1 inhibition is associated with non-progressive cognitive worsening that may be caused by modulation of unknown physiological BACE1 substrates. METHODS: To identify in vivo-relevant BACE1 substrates, we applied pharmacoproteomics to non-human-primate cerebrospinal fluid (CSF) after acute treatment with BACE inhibitors. RESULTS: Besides SEZ6, the strongest, dose-dependent reduction was observed for the pro-inflammatory cytokine receptor gp130/IL6ST, which we establish as an in vivo BACE1 substrate...
February 21, 2023: Molecular Neurodegeneration
Kristine M Tran, Shimako Kawauchi, Enikö A Kramár, Narges Rezaie, Heidi Yahan Liang, Jasmine S Sakr, Angela Gomez-Arboledas, Miguel A Arreola, Celia da Cunha, Jimmy Phan, Shuling Wang, Sherilyn Collins, Amber Walker, Kai-Xuan Shi, Jonathan Neumann, Ghassan Filimban, Zechuan Shi, Giedre Milinkeviciute, Dominic I Javonillo, Katelynn Tran, Magdalena Gantuz, Stefania Forner, Vivek Swarup, Andrea J Tenner, Frank M LaFerla, Marcelo A Wood, Ali Mortazavi, Grant R MacGregor, Kim N Green
BACKGROUND: The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer's Disease (AD). Unfortunately, many current Trem2 R47H mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2R47H NSS (Normal Splice Site) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products...
February 17, 2023: Molecular Neurodegeneration
Ahmed Haider, Nehal H Elghazawy, Alyaa Dawoud, Catherine Gebhard, Thomas Wichmann, Wolfgang Sippl, Marius Hoener, Ernest Arenas, Steven H Liang
Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects elderly people and constitutes a major source of disability worldwide. Notably, the neuropathological hallmarks of PD include nigrostriatal loss and the formation of intracellular inclusion bodies containing misfolded α-synuclein protein aggregates. Cardinal motor symptoms, which include tremor, rigidity and bradykinesia, can effectively be managed with dopaminergic therapy for years following symptom onset. Nonetheless, patients ultimately develop symptoms that no longer fully respond to dopaminergic treatment...
February 10, 2023: Molecular Neurodegeneration
Kathrin Wenger, Arthur Viode, Christoph N Schlaffner, Patrick van Zalm, Long Cheng, Tammy Dellovade, Xavier Langlois, Anthony Bannon, Rui Chang, Theresa R Connors, Derek Oakley, Bernhard Renard, Juri Rappsilber, Bradley Hyman, Hanno Steen, Judith A Steen
BACKGROUND: Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer's Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level. METHODS: We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics...
February 2, 2023: Molecular Neurodegeneration
Sidhanth Chandra, Sangram S Sisodia, Robert J Vassar
Alzheimer's disease (AD), the most common cause of dementia, results in a sustained decline in cognition. There are currently few effective disease modifying therapies for AD, but insights into the mechanisms that mediate the onset and progression of disease may lead to new, effective therapeutic strategies. Amyloid beta oligomers and plaques, tau aggregates, and neuroinflammation play a critical role in neurodegeneration and impact clinical AD progression. The upstream modulators of these pathological features have not been fully clarified, but recent evidence indicates that the gut microbiome (GMB) may have an influence on these features and therefore may influence AD progression in human patients...
February 1, 2023: Molecular Neurodegeneration
Wenhui Qiao, Yixing Chen, Jun Zhong, Benjamin J Madden, Cristine M Charlesworth, Yuka A Martens, Chia-Chen Liu, Joshua Knight, Tadafumi C Ikezu, Kurti Aishe, Yiyang Zhu, Axel Meneses, Cassandra L Rosenberg, Lindsey A Kuchenbecker, Lucy K Vanmaele, Fuyao Li, Kai Chen, Francis Shue, Maxwell V Dacquel, John Fryer, Akhilesh Pandey, Na Zhao, Guojun Bu
BACKGROUND: The rare p.H157Y variant of TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) was found to increase Alzheimer's disease (AD) risk. This mutation is located at the cleavage site of TREM2 extracellular domain. Ectopic expression of TREM2-H157Y in HEK293 cells resulted in increased TREM2 shedding. However, the physiological outcomes of the TREM2 H157Y mutation remain unknown in the absence and presence of AD related pathologies. METHODS: We generated a novel Trem2 H157Y knock-in mouse model through CRISPR/Cas9 technology and investigated the effects of Trem2 H157Y on TREM2 proteolytic processing, synaptic function, and AD-related amyloid pathologies by conducting biochemical assays, targeted mass spectrometry analysis of TREM2, hippocampal electrophysiology, immunofluorescent staining, in vivo micro-dialysis, and cortical bulk RNA sequencing...
January 31, 2023: Molecular Neurodegeneration
Kassandra Kisler, Abhay P Sagare, Divna Lazic, Sam Bazzi, Erica Lawson, Ching-Ju Hsu, Yaoming Wang, Anita Ramanathan, Amy R Nelson, Zhen Zhao, Berislav V Zlokovic
BACKGROUND: PICALM is one of the most significant susceptibility factors for Alzheimer's disease (AD). In humans and mice, PICALM is highly expressed in brain endothelium. PICALM endothelial levels are reduced in AD brains. PICALM controls several steps in Aβ transcytosis across the blood-brain barrier (BBB). Its loss from brain endothelium in mice diminishes Aβ clearance at the BBB, which worsens Aβ pathology, but is reversible by endothelial PICALM re-expression. Thus, increasing PICALM at the BBB holds potential to slow down development of Aβ pathology...
January 27, 2023: Molecular Neurodegeneration
Guojun Bu, Hui Zheng
No abstract text is available yet for this article.
January 26, 2023: Molecular Neurodegeneration
Katarina Stoklund Dittlau, Lisanne Terrie, Pieter Baatsen, Axelle Kerstens, Lim De Swert, Rekin's Janky, Nikky Corthout, Pegah Masrori, Philip Van Damme, Poul Hyttel, Morten Meyer, Lieven Thorrez, Kristine Freude, Ludo Van Den Bosch
BACKGROUND: Astrocytes play a crucial, yet not fully elucidated role in the selective motor neuron pathology in amyotrophic lateral sclerosis (ALS). Among other responsibilities, astrocytes provide important neuronal homeostatic support, however this function is highly compromised in ALS. The establishment of fully human coculture systems can be used to further study the underlying mechanisms of the dysfunctional intercellular interplay, and has the potential to provide a platform for revealing novel therapeutic entry points...
January 18, 2023: Molecular Neurodegeneration
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.