Alzheimer's disease: β‐amyloid plaque formation in human brain

Abstract

Although the precise cause of Alzheimer's disease is not known, the β-amyloid peptide chains of 40-42 amino acids are suspected to contribute to the disease. The β-amyloid precursor protein is found on many types of cell membranes, and the action of secretases (β and γ) on this precursor protein normally releases the β-amyloids at a high rate into the plasma and the cerebrospinal fluid. However, the concentrations of the β-amyloids in the plasma and the spinal fluid vary considerably between laboratories. The β-amyloids adsorb in the nanomolar concentration range to receptors on neuronal and glial cells. The β-amyloids are internalized, become folded in the β-folded or β-pleated shape, and then stack on each other to form long fibrils and aggregates known as plaques. The β-amyloids likely act as monomers, dimers, or multimers on cell membranes to interfere with neurotransmission and memory before the plaques build up. Treatment strategies include inhibitors of β- and γ-secretase, as well as drugs and physiological compounds to prevent aggregation of the amyloids. Several immune approaches and a cholesterol-lowering strategy are also being tested to remove the β-amyloids.

Beauty of Fine Dots-Detection and Treatment of Alzheimer's Disease Using CdSe/ZnS Quantum Dots

“…A number of potential pathologies could be caused by nanoparticles, like that in respiratory, cardiovascular and gastrointestinal system [3]. Because of this problem, with the use of nanoparticles and growing funding for many researches of this type, a new discipline in science arose and that is nanotoxicology [15]. Also there is a lack of standardize protocols for testing their possible toxic impact on biologic systems [16].…”

“…Some studies have shown that the toxicity of the QDs is size and concentration related and that CdSe quantum dots are toxic and aren't suitable for medical purposes, but with the ZnS coating it was proven a significant decrease in toxicity in cell culture [15].…”

“…Do they affect the brain [2]? Many studies must be carried out for the use of nanoparticles in humans, because known experiments were made only on animal models and in vitro and the effect on human system is difficult to evaluate from these kinds of researches [15]. For example, in 2013 researchers showed that QD-based imaging conducted on a monkey model showed no adverse effects, giving the fact that the QDs accumulated themselves in lymph nodes, bone marrow, spleen and liver up to 3 months after injection [18].…”

Evaluación de la enfermedad de Alzheimer en etapa temprana: biomarcadores y pruebas neuropsicológicas

“…Aβ es producto de la proteína precursora de amiloide (APP) que es clivada por proteasas (secretasas α, β, γ); el sitio de clivaje determinará el origen de varias isoformas de Aβ que tienen entre 36 y 43 aminoácidos. Investigaciones recientes han asociado la isoforma Aβ 42 en la formación de placas amiloideas 14 . Si bien son numerosos los mecanismos que definen a Aβ como el principal responsable de la muerte neuronal (activación de microglias, aumento de citoquinas neurotóxicas, daño oxidativo, etc.…”

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

“…NTF deficiency has the same presentation as the end-point of AD, neuronal loss and synaptic dysfunction. Regionalized neuronal death/loss and synaptic impairment in the process of AD have been demonstrated in many diagnostic, clinical, and pathological studies [56][57][58][59] . For example, West et al [60] found that neurons in the CA1 region of the hippocampus decline from 14.08 × 10 6 neurons in an age-matched control group to 4.40 × 10 6 neurons in an AD group.…”