Alzheimer's disease mechanisms in peripheral cells: Promises and challenges

Abstract

Introduction Development of efficacious therapeutic interventions for Alzheimer's disease (AD) is hampered by the lack of understanding early disease mechanisms, biomarkers, and models that mimic complex pathophysiology of human disease. Methods This article aims to assess to what extent peripheral cells recapitulate molecular mechanisms altered in the brain and could be used as translational models for the development of individualized medicine for AD. Results Multiple studies suggest that AD is a systemic disorder with an active crosstalk between brain and periphery where multiple pathways altered in the brain cells are also affected in plasma, cerebrospinal fluid, and other peripheral cells of AD patients. Discussion Additional studies to validate molecular mechanisms in peripheral cells using advanced system biology techniques and well‐characterized cohorts of AD patients together with the development of standardized protocols should be considered to support the application of peripheral cells in AD research.

Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover

“…In our study, we used primary dermal fibroblasts from sAD patients. It was demonstrated that AD-related pathological changes are not limited to neurons, but can also be observed in peripheral cells, including fibroblasts [23,37]. In contrast to postmortem brain specimens, fibroblast cultures allow us to investigate the earlier stages of disease development and to analyze vital cellular processes.…”

“…An increasing number of reports have shown that mitochondrial dysfunction is an early event in AD development [10,18,19] and that this dysfunction is not limited to neurons, but may also be observed in the peripheral tissues of AD patients [20][21][22][23][24]. Alterations in mitochondrial homeostasis affect multiple aspects of cellular function, including calcium handling, redox homeostasis and metabolism.…”

Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease

“…This limitation potentially leads to wrong conclusions about the pathogenic mechanisms and ultimately may dampen the development of effective therapies. Alternatively, patient-derived cells of neuronal lineage such as those from the olfactory epithelium may provide a convenient solution to this problem [5,9,42]. On the other hand, the accumulation of superoxide anion increases the levels of compounds such as 4-hydroxynonenal (4-HNE).…”

“…Although the manifestations of AD are preponderantly cerebral, cumulative evidence shows that AD is a systemic disorder [5]. Accordingly, molecular changes associated with AD are not exclusively manifested in the brain but include cells from different parts of the body, ranging from the blood and skin to peripheral olfactory cells.…”

Update of Immunosenescence in Cerebral Small Vessel Disease

“…Aβ deposition interacts with glial cells, pericytes, and neurons, modifies BBB and leads to immune cell infiltration ( 49 ). Those infiltrated cells and inflammatory mediators induce a proinflammatory environment around the lesion, which eventually leads to neuroinflammation and neurodegeneration ( 50 , 51 ). Current study concluded that the systematic immune response also involves in the neuroinflammation for which there is a large amount of evidence suggesting a proinflammatory state in AD patient, which implicates the complicated influence of immunosenescence in this disease ( 50 ).…”