In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds.

Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses. We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages of tauopathy.

Astrocyte-derived MFG-E8 facilitates microglial synapse elimination in Alzheimer's disease mouse models.

Region-specific synapse loss is an early pathological hallmark in Alzheimer's disease (AD). Emerging data in mice and humans highlight microglia, the brain-resident macrophages, as cellular mediators of synapse loss; however, the upstream modulators of microglia-synapse engulfment remain elusive. Here, we report a distinct subset of astrocytes, which are glial cells essential for maintaining synapse homeostasis, appearing in a region-specific manner with age and amyloidosis at onset of synapse loss.

Author Correction: Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models.

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Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models.

Neuronal hyperactivity is a key feature of early stages of Alzheimer's disease (AD). Genetic studies in AD support that microglia act as potential cellular drivers of disease risk, but the molecular determinants of microglia-synapse engulfment associated with neuronal hyperactivity in AD are unclear. Here, using super-resolution microscopy, 3D-live imaging of co-cultures, and in vivo imaging of lipids in genetic models, we found that spines become hyperactive upon Aβ oligomer stimulation and externalize phosphatidylserine (ePtdSer), a canonical "eat-me" signal.

Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts.

Lipoteichoic acid and molecular weight of hyaluronic acid could explain the late inflammatory response trigger by hyaluronic acid fillers.

Introduction: Hyaluronic acid is a safe dermal filler, but sometimes late granuloma is generated. This adverse effect is an inflammatory process, and its causes are not clear. Late granuloma generation could be due to the reaction to residual components of the bacterial wall present into hyaluronic acid, such as lipoteichoic acid (LTA).

SFRP1 modulates astrocyte-to-microglia crosstalk in acute and chronic neuroinflammation.

Neuroinflammation is a common feature of many neurodegenerative diseases. It fosters a dysfunctional neuron-microglia-astrocyte crosstalk that, in turn, maintains microglial cells in a perniciously reactive state that often enhances neuronal damage. The molecular components that mediate this critical communication are not fully explored.

The Jekyll and Hyde of TREM2.

In a recent paper, Gratuze et al. demonstrated a putative neuroprotective role of a key Alzheimer risk variant, TREM2, against tau-mediated neurodegeneration in a mouse model of tauopathy. This study highlights the context-dependent response of microglia, and proposes antagonistic roles of TREM2 in Aβ- versus tau-mediated pathology.

Sfrp1 deficiency makes retinal photoreceptors prone to degeneration.

Millions of individuals worldwide suffer from impaired vision, a condition with multiple origins that often impinge upon the light sensing cells of the retina, the photoreceptors, affecting their integrity. The molecular components contributing to this integrity are however not yet fully understood. Here we have asked whether Secreted Frizzled Related Protein 1 (SFRP1) may be one of such factors.

Elevated levels of Secreted-Frizzled-Related-Protein 1 contribute to Alzheimer's disease pathogenesis.

The deposition of aggregated amyloid-β peptides derived from the pro-amyloidogenic processing of the amyloid precurson protein (APP) into characteristic amyloid plaques (APs) is distinctive to Alzheimer's disease (AD). Alternative APP processing via the metalloprotease ADAM10 prevents amyloid-β formation. We tested whether downregulation of ADAM10 activity by its secreted endogenous inhibitor secreted-frizzled-related protein 1 (SFRP1) is a common trait of sporadic AD.