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Alzheimer's disease (AD) is the most prevalent cause of dementia, affecting one in nine people aged 65 years and older worldwide. Pathological hallmarks include the accumulation of senile plaques and neurofibrillary tangles, which are associated with changes in the levels of AD biomarkers, such as amyloid peptides and tau proteins. As the neuropathological process of AD commences decades before the onset of cognitive symptoms, an accurate assessment of AD biomarkers is critical for the early identification of at-risk AD patients. Photoelectrochemical (PEC) bioanalysis is a promising sensing methodology that exhibits superior sensing performance owing to the complete separation of the excitation source and detection signal. Numerous efforts have been made to develop PEC analytical platforms that target AD biomarkers. This review provides an overview of the recent advances in PEC sensing of AD biomarkers in body fluids. The major components of PEC sensing platforms (such as photoactive transducers, affinity agents, and targeted AD biomarkers) and PEC signaling strategies for detecting AD biomarkers are outlined. In addition, we summarize the current issues and strategies for advancing PEC sensing techniques to meet the ever-increasing demand for the early diagnosis of AD. [ABSTRACT FROM AUTHOR]

The region 1–16 of the amyloid-β peptides associated with Alzheimer's disease can be considered as the metal-binding domain, and the residues His6, His13, and His14 have been identified as ligands that coordinate heavy metal ions. To establish the role played by the three histidine residues of the Aβ(1–16) sequence in binding metal ions, two variants of Aβ(1–16) peptide fragment (H-1DAEFRHDSGYEVHHQK16-NH2) were synthesized by Fmoc/tBu Solid Phase Peptide Synthesis strategy and purified by RP-HPLC. The three histidine residues were replaced by either three serine residues to form Ser-Aβ(1–16): H-1DAEFRSDSGYEVSSQK16-NH2 or three alanine ones to form Ala–Aβ(1–16): H-1DAEFRADSGYEVAAQK16-NH2. The three peptides were comparatively characterized by mass spectrometry (MS), circular dichroism spectroscopy (CD) and atomic force microscopy (AFM), being subsequently used to study their interaction with metal ions at various pH values. During our experiments, significant pH-dependent changes in the conformation of these peptides have been observed and reported. AFM images showed dramatic changes in the film morphology of peptides upon binding metal ions. In the MS spectra we have unambiguously identified several metal–peptide molecular ions, thus confirming the affinity of Aβ(1–16) peptides to copper and nickel ions. The newly synthesized peptides may bring new evidence on the relationship of histidine residues in amyloid-β peptides with metal ions. In addition, new directions for research and experimental works are suggested. [ABSTRACT FROM AUTHOR]

Heavy metal ions and those of aluminum may interact with amyloid-β peptides (Αβ) associated with Alzheimer's disease, contributing to Aβ aggregation and fibrillation that worsen this neuropathology. Nevertheless, the precise residues involved in metal ligation or interaction are yet to be established, although the N-terminal Aβ(1–16) peptide fragment is considered to be the metal-binding domain. However, because the results of the metal ion binding studies using Aβ(1–16) were not very conclusive, we have investigated shorter peptides. Here, we report the synthesis of truncated Aβ(9–16) peptide of the human Aβ(1–40) and Aβ(1–42) peptides, as well as its characterization by nuclear magnetic resonance and mass spectrometry. Furthermore, the Aβ(9–16) peptide interactions with various metal ions like Cu2+, Zn2+, Fe3+, Al3+, and Ni2+ were studied by circular dichroism, Fourier transform-infrared, and fluorescence spectroscopy. Our results show that the newly synthesized peptide sequence, which contains just two histidine and one tyrosine residues, seems to be a key site for metal binding, which was not thoroughly investigated so far. Light scattering spectra of Aβ(9–16) and its complexes with metal ions were measured, whereas some fluorescence experiments were also performed. Our data suggest that Aβ(9–16) peptide fragment coordination by metal ions is dependent on the type of metal, and the amino acid residues involved in metal bonding. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by excessive accumulation of the amyloid-β peptide (Aβ) in the brain, which has been considered to mediate the neuroinflammation process. Microglial activation is the main component of neuroimmunoregulation. In recent years, exosomes isolated from human umbilical cord mesenchymal stem cells (hucMSC-exosomes) have been demonstrated to mimic the therapeutic effects of hucMSCs in many inflammation-related diseases. In this study, exosomes from the supernatant of hucMSCs were injected into AD mouse models. We observed that hucMSC-exosomes injection could repair cognitive disfunctions and help to clear Aβ deposition in these mice. Moreover, we found that hucMSC-exosomes injection could modulate the activation of microglia in brains of the mice to alleviated neuroinflammation. The levels of pro-inflammatory cytokines in peripheral blood and brains of mice were increased and the levels of anti-inflammatory cytokines were decreased. We also treated BV2 cells with hucMSC-exosomes in culture medium. HucMSC-exosomes also had inflammatory regulating effects to alternatively activate microglia and modulate the levels of inflammatory cytokines in vitro. [ABSTRACT FROM AUTHOR]

Aggregation of amyloid-β (Aβ) peptides, which are the cleavage products of amyloid precursor protein (APP), is a major pathological hallmark in the brain of Alzheimer’s disease (AD). Now, we know little about the roles of APP translation in the disease progression of AD. Here, we show that BC1, a long noncoding RNA (lncRNA), is expressed in the brain of AD mice. BC1 induces APP mRNA translation via association with a fragile X syndrome protein (FMRP). Inhibition of BC1 or BC1-FMRP association in AD mice blocks aggregation of Aβ in the brain and protects against the spatial learning and memory deficits. Expression of exogenous BC1 in excitatory pyramidal neurons of mice induces Aβ peptides accumulation and the spatial learning and memory impairments. This study provides a novel mechanism underlying aggregation of Aβ peptides via BC1 induction of APP mRNA translation and hence warrants a promising target for AD therapy. [ABSTRACT FROM AUTHOR]

Amyloid-β peptides (Aβ), a major component of senile plaques, play an important role in the development and progression of Alzheimer's disease. Several lines of evidence have demonstrated that Aβ-induced neuronal death is mediated by oxidative stress. The present study aimed to evaluate the potential involvement of di- O-demethylcurcumin, an analog of curcuminoid, on Aβ-induced neurotoxicity in culture neuroblastoma cells (SK-N-SH cells) through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the suppression of nuclear factor-κB (NF-κB) signaling pathway and their downstream targets. The results showed that pretreatment with di- O-demethylcurcumin elevated cell viability and decreased the level of reactive oxygen species. Moreover, treatment with di- O-demethylcurcumin promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus, increased the expression of Nrf2-ARE pathway-related downstream proteins including heme oxygenase (HO-1), NAD(P)H:quinone oxidoreductase 1 and glutamate-cysteine ligase catalytic subunit, and increased the activity of superoxide dismutase enzymes. On the other hand, di- O-demethylcurcumin suppressed the degradation of IκBα, translocation of the p65 subunit of NF-κB from cytoplasm to nucleus and thereby, attenuated the expression of inducible nitric oxide synthase protein and nitric oxide production. Taken together, these results suggest that neuroinflammatory effect of di- O-demethylcurcumin might potentially be due to inhibit NF-κB and activate Nrf2 signaling pathways induced by Aβ. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is characterized by Amyloid-β (Aβ) deposition in senile plaques in specific areas of the brain and by intraneuronal p-tau accumulation in neurofibrillary tangles. Cumulative evidence supports that oxidative stress is an important factor in the pathogenesis of AD and contributes to Aβ generation. However, there is no effective treatment for AD. Human umbilical cord mesenchymal stem cells (HUMSCs) have potential therapeutic value for the treatment of neurological disease. However, the therapeutic impact of systemic administration of HUMSCs and their mechanism of action in AD have not yet been determined. Here, we found that intravenous infusion of HUMSCs significantly improved spatial learning and alleviated memory decline in an AβPP/PS1 mouse model of AD. HUMSC treatment also increased glutathione (GSH) activity and ratio of GSH to oxidative glutathione as well as superoxide dismutase activity, while decreasing malondialdehyde activity and protein carbonyl level, which suggests that HUMSC infusion alleviated oxidative stress in AβPP/PS1 mice. In addition, HUMSC infusion reduced β-secretase 1 and CTFβ, thus reducing Aβ deposition in mice. HUMSCs may have beneficial effects in the prevention and treatment of AD. [ABSTRACT FROM AUTHOR]

Alzheimer's dementia (AD) and frontotemporal dementias (FTD) are common and their clinical differential diagnosis may be complicated by overlapping symptoms, which is why biomarkers may have an important role to play. Cerebrospinal fluids (CSF) Aβ2-42 and 1-42 have been shown to be similarly decreased in AD, but 1-42 did not display sufficient specificity for exclusion of other dementias from AD. The objective of the present study was to clarify the diagnostic value of Aβ2-42 peptides for the differential diagnosis of AD from FTD. For this purpose, 20 non-demented disease controls (NDC), 22 patients with AD and 17 with FTD were comparatively analysed by a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol with subsequent Aβ-SDS-PAGE/immunoblot, allowing the quantification of peptides 1-38, 2-40 and 2-42 along with Aβ 1-37, 1-38, 1-39, 1-40, 1-40 and 1-42. CSF Aβ1-42 was decreased in AD as compared to NDC, but not to FTD. In a subgroup of the patients analyzed, the decrease of Abeta2-42 in AD was evident as compared to both NDC and FTD. Aβ1-38 was decreased in FTD as compared to NDC and AD. For differentiating AD from FTD, Aβ1-42 demonstrated sufficient diagnostic accuracies only when combined with Aβ1-38. Aβ2-42 yielded diagnostic accuracies of over 85 % as a single marker. These accuracy figures could be improved by combining Aβ2-42 to Aβ1-38. Aβ2-42 seems to be a promising biomarker for differentiating AD from other degenerative dementias, such as FTD. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) 1-38, 1-40, 1-42, total-tau and phospho-tau in samples from 156 patients with Alzheimer’s disease (AD) ( n = 44), depressive cognitive complainers (DCC, n = 25) and various other forms of non-Alzheimer dementias (NAD, n = 87) were analyzed by electrochemiluminescence and enzyme linked immunosorbent assay, respectively. A significant decrease of CSF Aβ1-42 was the most powerful single marker for differentiation of AD from DCC, yielding accuracies of beyond 85%. Increased p-tau and the ratio Aβ1-42/Aβ1-38 yielded accuracies of beyond 80 and 85%, respectively, to discriminate AD versus NAD. Combining p-tau with Aβ1-42/Aβ1-38 resulted in a sensitivity of 94% for detection of AD and 85% specificity for excluding NAD. Decreased CSF Aβ1-42 represents a core biomarker for AD. The lack of specificity for exclusion of NAD can be most effectively compensated by the ratio Aβ1-42/Aβ1-38. The ratio Aβ1-42/Aβ1-38/p-tau powerfully discriminates AD versus NAD and fulfils the accuracy requirements for an applicable screening and differential diagnostic AD biomarker. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) carboxyterminally truncated amyloid-beta (Aβ) peptides, Aβ1-42 and tau protein were evaluated in 30 patients with frontotemporal lobe degenerations (FTLD), 30 Alzheimer’s disease (AD) patients and 30 non-demented disease controls (NDC) by Aβ-SDS-PAGE/immunoblot as well as commercial ELISAs for Aβ1-42 and total tau. FTLD displayed a significant drop of Aβ1-37 (p = 2.7 × 10−4), Aβ1-38 (p = 4.2 × 10−5) and Aβ1-42 (p = 3.3 × 10−4). Aβ1-42 was selectively decreased in AD (p = 8.5 × 10−10). Decreased Aβ1-38 enabled contrasts of beyond 85% to distinguish FTLD from AD and NDC patients, alone or in combination. Accordingly, low CSF Aβ1-37 and Aβ1-38 represent a biomarker candidate for FTLD and may reflect disease-specific changes of APP metabolism. Further validation should be carried out on dementias other than AD, diagnostically relevant control groups without dementia and without any evident affection of the central nervous system and subgroups of FTLD. Moreover, independent methods of measurement should be applied to CSF Aβ1-38. [ABSTRACT FROM AUTHOR]