ABSTRACT
Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that-upon engagement of pattern recognition receptors-induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.
Subject(s)
Alzheimer Disease/drug therapy , Inflammation/drug therapy , Molecular Targeted Therapy , Alzheimer Disease/immunology , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/metabolism , Animals , Humans , Immunity, Innate/immunology , Inflammation/immunology , Inflammation/physiopathologyABSTRACT
OBJECTIVES: Biomarker quest for Alzheimer's disease (AD) has gone a long way by studying various anatomical, physiological and biochemical parameters for detecting disease onset and predicting prognosis. Almost all the studies converge on the single hypothesis of the amyloid and Tau pathway. Recently, vascular hypothesis has evolved drawing attention towards a complex dynamic anatomical and physiological entity, neuro-vascular (NV) unit. Pathological changes at this level, altering the normal physiology such as auto-regulation and dynamics of blood brain barrier have been hypothesized as a probable basis for AD. This paper attempts to review the existing data on the vascular hypothesis and the current trends in analyzing the NV unit in AD. DESIGN: This review initially focuses on the cerebral NV coupling followed by the retinal neurovascular coupling that mirrors the cerebral pathophysiology. The pathophysiology and the potential tools to diagnose AD at the level of NV unit are analyzed. Further, it examines the drawbacks in existing methods for analyzing the same. FINDINGS: None of the current studies have emphasized the importance of studying the complex dynamic NV unit as a whole. This review strongly recommends the combination of vascular and neuro-glial parameters using objective methods for estimating the physiological and pathological changes in the NV unit. DISCUSSION AND CONCLUSION: This review highlights the importance of retina for non-invasive estimation of the same. Also, novel algorithms for retinal image analysis have been proposed. The purpose of this review is to highlight the importance of retinal findings in neurodegenerative disorders and to create awareness among the neuroophthalmologists, of the potential benefits of ophthalmological tools in screening dementia patients.
