The extent of Lead‐induced Pathogenesis of Alzheimer’s disease, Synaptic Dysfunction and Cognitive Impairment in Rats

Abstract Background The hallmarks of Alzheimer’s disease (AD), like amyloid plaques and neurofibrillary tangles, are constituted of amyloid beta (Aβ) peptide and phosphorylated tau, respectively. Many studies reported the relationship between lead exposure and the progression of AD. However, the extent of lead‐induced pathogenesis and changes in proteins regulating synaptic plasticity in AD is lacking. The proposed study is designed to evaluate the pathogenesis of AD, synaptic dysfunction and cognitive impairment following lead exposure in rats. Method Thirty (30) Wistar rats (3 weeks old) will be obtained, acclimatized for one week, and randomly divided into five groups (n = 6). The rats will receive distilled deionized water containing 0% lead acetate [Pb 2+ ] (ddH 2 O) or 0.5% [Pb 2+ ] (ddH 2 O + 0.5% Pb 2+ ) solution with a standard rat diet. Group I (baseline) will receive ddH 2 O for three (3) weeks. Group II (control) will receive ddH 2 O for nine (9) weeks. Groups III, IV, and V will receive (ddH 2 O + 0.5% Pb 2+ ) solution for 3, 6, and 9 weeks respectively. Cognitive function will be conducted using 8‐ARWM as well as object recognition tests. The hippocampus will be extracted for immunohistochemical and biochemical studies. The levels of β‐secretase, Aβ 42 , tau protein (p‐tau), NMDAR subunit NR2B, postsynaptic density protein 95 (PSD‐95), Synaptophysin (SYP), and brain‐derived neurotrophic factor (BDNF) will be determined using Enzyme‐linked immunosorbent assay (ELISA) method. The expression levels of Aβ 42 , neurofibrillary tangle (NFT), NR2B, PSD‐95, and SYN will be determined using the immunohistochemical method. The expression of β‐secretase and BDNF will be determined using quantitative real‐time PCR. Result Lead could affect the levels of β‐secretase, Aβ 42 , p‐tau, NR2B, PSD‐95, SYP BDNF; the expression of Aβ 42 , NFT, NR2B, PSD‐95, SYN, and BDNF; and cognitive function. Conclusion The results could reveal the extent to which lead‐induced pathogenesis, synaptic dysfunction and cognitive impairment in AD