Oxidative stress in Alzheimer’s disease

Abstract

Oxidative balance is emerging as an important issue in understanding the pathogenesis of Alzheimer's disease. Examination of Alzheimer's disease brain has demonstrated a great deal of oxidative damage, associated with both hallmark pathologies (senile plaques and neurofibrillary tangles) as well as in normal appearing pyramidal neurons. While this suggests that oxidative stress is a proximal event in Alzheimer's disease pathogenesis, the mechanisms by which redox balance is altered in the disease remains elusive. Determining which of the proposed sources of free radicals, which include mitochondrial dysfunction, amyloid-beta-mediated processes, transition metal accumulation and genetic factors like apolipoprotein E and presenilins, is responsible for redox imbalance will lead to a better understanding of Alzheimer's disease pathogenesis and novel therapeutic approaches.

Localization of the noncovalent binding site between amyloid-β-peptide and oleuropein using electrospray ionization FT-ICR mass spectrometry

“…When OE was added into already digested A␤ samples with trypsin ( Similarly, ESI-MS analysis of the A␤-OE Glu-C digest yielded signals corresponding to the expected A␤ fragments [4 -11], [12][13][14][15][16][17][18][19][20][21][22], and [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] following cleavage at the carboxy-terminus of glutamic acid (E) residues (Table 2), and the noncovalent complexes between OE and the [4 -11] and [12][13][14][15][16][17][18][19][20][21][22] A␤ Glu-C fragments ( Figure 3). Interactions between OE and the partially cleaved peptide fragments [4 -40] and (Table 4) When OE was added into already digested A␤ samples with Glu-C (Table 4), ESI signals corresponded to ...…”

“…Free radical reactions and oxidative stress [28,29], as well as unregulated immune response [30,31], are believed to be key factors for the pathogenesis of AD, whereas recent reports suggested a link between heart disease, hypercholesterolemia, and…”

“…Free radical reactions and oxidative stress [28,29], as well as unregulated immune response [30,31], are believed to be key factors for the pathogenesis of AD, whereas recent reports suggested a link between heart disease, hypercholesterolemia, and AD [32,33]. Thus, the well-documented antioxidant, anti-inflammatory, and antiatherogenic properties of OE may offer a multistage approach against the diverse mechanisms, which are inherent to AD.…”

Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease

“…Oxidative stress is also reported to play a role in the process of AD, as strongly proposed by Smith and Perry [89,90] , and antioxidants may be associated with a lower risk of AD [91] . These treatment strategies for AD are still under way and more investigations and trials are needed to test their efficacy in its prevention or treatment.…”

“…Barthel et al, using positron emission tomography (PET) images of florbetaben (an 18 F-labeled Aβ-targeted PET tracer), demonstrated that nine of ten mildmoderate probable AD participants (DSM-IV and NINCDS-ADRDA criteria) were Aβ-positive, compared to only one of ten healthy controls [49] . Furthermore, in a global phase 2, open-label, non-randomized, multi-center study recruiting a total of 81 men and women with probable mild-to-moderate AD and 69 cognitively unimpaired healthy volunteers aged 55 years and older, florbetaben scans indicated a sensitivity of 80% (95% CI 71-89) and a specificity of 91% (84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98) for discriminating participants with AD from healthy controls [50] .…”