Seed-induced Aβ deposition alters neuronal function and impairs olfaction in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) which ultimately forms plaques. These Aβ deposits can be induced in APP transgenic mouse models by prion-like seeding. It has been widely accepted that anosmia and hyposmia occur during the early stages of AD, even before cognitive deficits are present.

Microglia contribute to the propagation of Aβ into unaffected brain tissue.

Microglia appear activated in the vicinity of amyloid beta (Aβ) plaques, but whether microglia contribute to Aβ propagation into unaffected brain regions remains unknown. Using transplantation of wild-type (WT) neurons, we show that Aβ enters WT grafts, and that this is accompanied by microglia infiltration. Manipulation of microglia function reduced Aβ deposition within grafts.

Distinct Aβ pathology in the olfactory bulb and olfactory deficits in a mouse model of Aβ and α-syn co-pathology.

Several degenerative brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by the simultaneous appearance of amyloid-β (Aβ) and α-synuclein (α-syn) pathologies and symptoms that are similar, making it difficult to differentiate between these diseases. Until now, an accurate diagnosis can only be made by postmortem analysis. Furthermore, the role of α-syn in Aβ aggregation and the arising characteristic olfactory impairments observed during the progression of these diseases is still not well understood.

Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma.

Background: Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between network architecture and transcriptional profile remains poorly investigated. Drugs that interfere with this syncytial connectivity such as meclofenamate (MFA) may be highly attractive for glioblastoma therapy.

Detection of Synaptic Proteins in Microglia by Flow Cytometry.

A growing body of evidence indicates that microglia actively remove synapses , thereby playing a key role in synaptic refinement and modulation of brain connectivity. This phenomenon was mainly investigated in immunofluorescence staining and confocal microscopy. However, a quantification of synaptic material in microglia using these techniques is extremely time-consuming and labor-intensive.

Mechanisms of Pathogenic Tau and Aβ Protein Spreading in Alzheimer's Disease.

Alzheimer's disease (AD) is pathologically defined by extracellular accumulation of amyloid-β (Aβ) peptides generated by the cleavage of amyloid precursor protein (APP), strings of hyperphosphorylated Tau proteins accumulating inside neurons known as neurofibrillary tangles (NFTs) and neuronal loss. The association between the two hallmarks and cognitive decline has been known since the beginning of the 20th century when the first description of the disease was carried out by Alois Alzheimer. Today, more than 40 million people worldwide are affected by AD that represents the most common cause of dementia and there is still no effective treatment available to cure the disease.

Author Correction: Novel Hexb-based tools for studying microglia in the CNS.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology.

When it comes to the human brain, models that closely mimic in vivo conditions are lacking. Living neuronal tissue is the closest representation of the in vivo human brain outside of a living person. Here, we present a method that can be used to maintain therapeutically resected healthy neuronal tissue for prolonged periods without any discernible changes in tissue vitality, evidenced by immunohistochemistry, genetic expression, and electrophysiology.

A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves.

The skin comprises tissue macrophages as the most abundant resident immune cell type. Their diverse tasks including resistance against invading pathogens, attraction of bypassing immune cells from vessels, and tissue repair require dynamic specification. Here, we delineated the postnatal development of dermal macrophages and their differentiation into subsets by adapting single-cell transcriptomics, fate mapping, and imaging.

Environmental enrichment reverses Aβ pathology during pregnancy in a mouse model of Alzheimer's disease.

Several studies suggest that women have a higher risk to develop Alzheimer's disease (AD) than men. In particular, the number of pregnancies was shown to be a risk factor for AD and women with several pregnancies on average had an earlier onset of the disease, thus making childbearing a risk factor. However, the impact of being pregnant on Aβ plaque pathology and adult neurogenesis still remains elusive.

Seed-induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by severe neuronal loss as well as the accumulation of amyloid-β (Aβ), which ultimately leads to plaque formation. Although there is now a general agreement that the aggregation of Aβ can be initiated by prion-like seeding, the impact and functional consequences of induced Aβ deposits (Aβ seeding) on neurons still remain open questions. Here, we find that Aβ seeding, representing early stages of plaque formation, leads to a dramatic decrease in proliferation and neurogenesis in two APP transgenic mouse models.

Selective vulnerability of spinal and cortical motor neuron subpopulations in delta7 SMA mice.

Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss.

Human axonal survival of motor neuron (a-SMN) protein stimulates axon growth, cell motility, C-C motif ligand 2 (CCL2), and insulin-like growth factor-1 (IGF1) production.

Spinal muscular atrophy is a fatal genetic disease of motoneurons due to loss of full-length survival of motor neuron protein, the main product of the disease gene SMN1. Axonal SMN (a-SMN) is an alternatively spliced isoform of SMN1, generated by retention of intron 3. To study a-SMN function, we generated cellular clones for the expression of the protein in mouse motoneuron-like NSC34 cells.

Spinal muscular atrophy pathogenic mutations impair the axonogenic properties of axonal-survival of motor neuron.

The axonal survival of motor neuron (a-SMN) protein is a truncated isoform of SMN1, the spinal muscular atrophy (SMA) disease gene. a-SMN is selectively localized in axons and endowed with remarkable axonogenic properties. At present, the role of a-SMN in SMA is unknown.