Skip to main content
. 2018 Dec 9;19(12):3965. doi: 10.3390/ijms19123965

Figure 1.

Figure 1

Neurobiological processes leading to AD. Hypothesis concerning OS involvement in AD etiopathogenesis: β-amyloid peptide activates the pathways involved in reactive oxygen species (ROS) synthesis, leading to the increased amount of ROS (left side of the picture). Simultaneously β-amyloid accumulation leads to the antioxidant enzymes’ inhibition (SOD, CAT, GPx, and GR) (left side of the picture. This imbalance between ROS synthesis and antioxidant enzymes activities results in the oxidative stress (OS). Excessive oxidation processes result in tau protein hyperphosphorylation and β-amyloid peptide accumulation (gray arrow, left side of the picture). Tau (τ) protein hyperphosphorylation hypothesis: Under physiological conditions, τ protein is the major neuronal microtubule associated protein. It promotes the assembly of tubulin into stabilizes the microtubules (top picture in the central part of the figure). Under pathological conditions (i.e., OS) Tau becomes hyperphosphorylated. Pathologically-altered τ protein loses its ability to interact with microtubules, leading to disintegration of microtubules (gray arrow, central part of the picture). Hyperphosphorylated Tau is insoluble. Insolubility leads to polymerization into paired helical filaments (PHF), which, together with straight filaments (SF), form neurofibrillary tangles (gray arrow, central part of the picture). Amyloid β aggregation hypothesis: Amyloid precursor protein (APP) is an integral transmembrane protein expressed in many tissues. In AD patients, initial cleavage (by β-secretase) (brown arrow) of the APP results in the extracellular soluble fragment formation. Subsequent cleavage catalyzed by γ-secretase leads to the β-amyloid formation. γ-secretase consists of presenilin, nicastrin, anterior pharynx-defective 1 (APH-1), and presenilin enhancer 2 (PEN-2) β-amyloid, which is insoluble aggregates (right part of the picture, gray arrow) to form In subsequence senile plaques. Another APP derived cleavage product is AICD (the amyloid precursor protein intracellular domain) (green spherical elements). Different AICD levels may contribute to early etiopathological sequences in AD. The processes mentioned above lead to the fibrillary tangles formation, neuronal death and Alzheimer’s disease (three red arrows).