Bi-directional Association of Cerebrospinal Fluid Immune Markers with Stage of Alzheimer's Disease Pathogenesis.

Immune mechanisms may be important in the pathogenesis of Alzheimer's disease (AD). Yet, studies comparing cerebrospinal fluid (CSF) and plasma immune marker levels of healthy and demented individuals have yielded conflicting results. We analyzed CSF from 101 members of the parental history-positive PREVENT-AD cohort of healthy aging adults, and 237 participants without dementia from the initial cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI-1).

Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease.

Neuroinflammation is now recognized as a major etiological factor in neurodegenerative disease. Mononuclear phagocytes are innate immune cells responsible for phagocytosis and clearance of debris and detritus. These cells include CNS-resident macrophages known as microglia, and mononuclear phagocytes infiltrating from the periphery.

Amyloid Cascade into Clarity.

In a recent issue of Nature, Sevigny et al. (2016) report findings from a phase 1b clinical trial of aducanumab (a monoclonal antibody targeting misfolded amyloid-β peptides), revitalizing the "amyloid cascade hypothesis" and bringing mononuclear phagocytes center stage in the treatment of Alzheimer's disease.

Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats.

Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI) and high-angular resolution imaging (HARDI) are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI), composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm2 and applied it in transgenic Alzheimer rats (line TgF344-AD) that model the full clinico-pathological spectrum of the human disease.

MyD88 is dispensable for cerebral amyloidosis and neuroinflammation in APP/PS1 transgenic mice.

Activated microglia are associated with amyloid plaques in transgenic mouse models of cerebral amyloidosis and in human Alzheimer disease; yet, their implication in Alzheimer disease pathogenesis remains unclear. It has been suggested that microglia play dual roles depending on the context of activation, contributing negatively to disease pathogenesis by secreting proinflammatory innate cytokines or performing a beneficial role via phagocytosis of amyloid beta (Aβ) deposits. Toll-like receptors, most of which signal through the adaptor protein myeloid differentiation factor 88 (MyD88), have been suggested as candidate Aβ innate pattern recognition receptors.

A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aβ, and frank neuronal loss.

Alzheimer's disease (AD) is hallmarked by amyloid plaques, neurofibrillary tangles, and widespread cortical neuronal loss (Selkoe, 2001). The "amyloid cascade hypothesis" posits that cerebral amyloid sets neurotoxic events into motion that precipitate Alzheimer dementia (Hardy and Allsop, 1991). Yet, faithful recapitulation of all AD features in widely used transgenic (Tg) mice engineered to overproduce Aβ peptides has been elusive.

Microglia in Alzheimer's Disease: It's All About Context.

Neuroinflammation is now regarded as both an early event and prime mover in the pathobiology of Alzheimer disease (AD), a neurodegenerative disease that represents a growing public health threat. As the resident innate immune cells within the central nervous system, microglia are centrally positioned as key orchestrators of brain inflammation. It is now accepted that numerous forms of activated microglia exist.

An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice.

Huntington's disease-like-2 (HDL2) is a phenocopy of Huntington's disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology, and ubiquitin-positive nuclear inclusions (NIs).