Oxidative Stress and Aberrant Cell Cycle in Alzheimer’s Disease Lymphocytes: Diagnostic Prospects

Wojsiat, Joanna; Prandelli, Chiara; Laskowska-Kaszub, Katarzyna; Martín-Requero, Ángeles; Wojda, Urszula

doi:10.3233/jad-141977

Cited by 46 publications

(50 citation statements)

References 186 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondria extracted from AD lymphocytes also showed raised levels of protein oxidation markers: 3NT and protein carbonyls, as well as protein-bound HNE, a lipid peroxidation marker. This is in accordance with increased glutathione disulfide levels and lowered plasma levels of glutathione GSH observed in AD lymphocytes [46]. Furthermore, recent data showed that increased susceptibility to oxidative death of lymphocytes from AD patients correlates with dementia severity [50].…”

supporting

confidence: 82%

“…Surprisingly, multiple recent studies suggest that cell cycle proteins' aberrant re-expression and the reentry of the cell cycle may represent a pathological feature of mature AD neurons [52]. Research points out that rather than being a consequence of neurodegeneration, cell cycle re-entry is its cause, and consequently cell cycle regulatory proteins of G1/S phase checkpoint may develop into early AD biomarkers [46,53,54].…”

Section: Dysregulated Cell Cycle In Lymphocytesmentioning

confidence: 99%

“…Increased mitochondrial and oxidative stress markers reflect the pathological changes of AD brains. Furthermore, considerable mitochondrial dysfunction has been found in MCI lymphocytes, without any τ or Aβ pathology (reviewed in [46]). These data confirm that oxidative stress markers may potentially become markers for early AD diagnosis ( Figure 1C).…”

mentioning

confidence: 99%

“…Research points out that rather than being a consequence of neurodegeneration, cell cycle re-entry is its cause, and consequently cell cycle regulatory proteins of G1/S phase checkpoint may develop into early AD biomarkers [46,53,54].…”

mentioning

confidence: 99%

“…The contribution of B cells in AD pathology has therefore been underestimated. Presently, a growing body of data indicates that perturbations in B-cell immunoreactivity are also a feature of AD pathology [46].Overall, molecular alterations in blood lymphocytes correlate with disturbances in the AD immune system. An increasing amount of evidence suggests a role of peripheral immune cells in the pathological events that occur in the brain.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Search for Alzheimer's Disease Biomarkers in Blood Cells: Hypotheses-Driven Approach

et al. 2017

Self Cite

View full text Add to dashboard Cite

Current Alzheimer's disease (AD) diagnostics is based on cognitive testing, and detecting amyloid Aβ and τ pathology by brain imaging and assays of cerebrospinal fluid. However, biomarkers identifying complex pathways contributing to pathology are lacking, especially for early AD. Preferably, such biomarkers should be more cost-effective and present in easily available diagnostic tissues, such as blood. Here, we summarize the recent findings of potential early AD molecular diagnostic biomarkers in blood platelets, lymphocytes and erythrocytes. We review molecular alterations which refer to such main hypotheses of AD pathogenesis as amyloid cascade, oxidative and mitochondrial stress, inflammation and alterations in cell cycle regulatory molecules. The major advantage of such biomarkers is the potential ability to indicate individualized therapies in AD patients. Alzheimer's disease (AD) is the most prevalent age-related dementia worldwide and one of the major unmet, increasing medical and economic problems of the modern world. As of 2015, there were an estimated 46.8 million people with dementia worldwide. This number will increase to an estimated 74.7 million in 2030 [1].Among the neuropathological hallmarks of AD are: the progressive loss of brain neurons, synaptic degeneration and the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs) in such regions of the brain as the hippocampus, cortex and amygdala. Amyloid plaques consist mainly of 40-and 42-amino-acid Aβ peptides (Aβ40 and Aβ42). Peptides are proteolytic cleavage products of the Aβ protein precursor (APP) but with no fully elucidated biological function. NFTs are deposits of paired helical filaments composed mainly of hyperphosphorylated τ protein, a microtubule-stabilizing protein that maintains neuronal cell structure and axonal transport. Nevertheless, neither senile plaques nor NFTs are absolute hallmarks of AD dementia, because cognitively intact aged individuals may exhibit both pathological changes upon postmortem brain examination or as assessed by positron emission tomography amyloid and τ imaging agents (amyloid-PET and τ-PET) [2][3][4][5].Clinical AD manifests by aggravating dysfunction and weakening functional cognitive processes, linked to brain neuron loss that is both progressive and permanent [4], and that within several years leads to total dependence on the caregiver and eventually to death. Advances in our knowledge of AD have shown that clinical symptoms usually develop after a long preclinical pathogenic process, lasting for decades, making early AD detection in asymptomatic patients a subject of great interest [4,5]. Increasing proof demonstrates that the therapeutic methods' effectiveness is strictly contingent on the early diagnosis of AD, before the occurrence of massive neuron loss and dementia. This highlights the key importance of biochemical biomarkers for early AD diagnostics. AD diagnostics & demand for novel, improved biomarkersThe broadly accepted recommendations for AD diagnosis...

show abstract

supporting

confidence: 82%