Instead, a surprising number of the experimental manipulations which increase microglial activation lead to enhanced clearance of the amyloid deposits. Both the literature and new data presented here suggest

that either classical or alternative activation of microglia can lead to enhanced amyloid clearance. However, a limited number of studies comparing the same treatments in amyloid-depositing vs. tau-depositing mice find the opposite effects. Treatments that benefit amyloid pathology accelerate tau pathology. This observation argues strongly that potential treatments be tested for impact on both amyloid and tau pathology before consideration of testing in humans. “
“Cerebral small vessel disease (SVD) causes a fifth of all strokes plus diffuse brain damage leading to cognitive decline, physical disabilities and dementia. find more The aetiology and pathogenesis of SVD are unknown, but largely attributed to hypertension or microatheroma. We used the spontaneously

hypertensive stroke-prone rat (SHRSP), the closest spontaneous Selleckchem Cilomilast experimental model of human SVD, and age-matched control rats kept under identical, non-salt-loaded conditions, to perform a blinded analysis of mRNA microarray, qRT-PCR and pathway analysis in two brain regions (frontal and mid-coronal) commonly affected by SVD in the SHRSP at age five, 16 and 21 weeks. We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), from vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats. All were present at age 5 weeks thus predating blood pressure elevation. ‘Neurological’

and ‘inflammatory’ pathways were more affected than ‘vascular’ functional pathways. This set of defects, although individually modest, when acting in combination could explain the SHRSP’s susceptibility to microvascular and brain injury, compared with control rats. Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD. “
“Failure of elimination of proteins from the brain is a major feature in many neurodegenerative diseases. Insoluble proteins accumulate in brain parenchyma and in walls of cerebral capillaries and arteries. Cerebral amyloid angiopathy (CAA) is a descriptive term for amyloid in vessel walls. Here, we adopt the term protein elimination failure angiopathy (PEFA) to focus on mechanisms involved in the pathogenesis of a spectrum of disorders that exhibit both unique and common features of protein accumulation in blood vessel walls.