| First Author | Tropea MR | Year | 2021 |
| Journal | Prog Neurobiol | Volume | 206 |
| Pages | 102154 | PubMed ID | 34453977 |
| Mgi Jnum | J:350407 | Mgi Id | MGI:7660894 |
| Doi | 10.1016/j.pneurobio.2021.102154 | Citation | Tropea MR, et al. (2021) Genetic deletion of alpha7 nicotinic acetylcholine receptors induces an age-dependent Alzheimer's disease-like pathology. Prog Neurobiol 206:102154 |
| abstractText | The accumulation of amyloid-beta peptide (Abeta) and the failure of cholinergic transmission are key players in Alzheimer's disease (AD). However, in the healthy brain, Abeta contributes to synaptic plasticity and memory acting through alpha7 subtype nicotinic acetylcholine receptors (alpha7nAChRs). Here, we hypothesized that the alpha7nAChR deletion blocks Abeta physiological function and promotes a compensatory increase in Abeta levels that, in turn, triggers an AD-like pathology. To validate this hypothesis, we studied the age-dependent phenotype of alpha7 knock out mice. We found that alpha7nAChR deletion caused an impairment of hippocampal synaptic plasticity and memory at 12 months of age, paralleled by an increase of Amyloid Precursor Protein expression and Abeta levels. This was accompanied by other classical AD features such as a hyperphosphorylation of tau at residues Ser 199, Ser 396, Thr 205, a decrease of GSK-3beta at Ser 9, the presence of paired helical filaments and neurofibrillary tangles, neuronal loss and an increase of GFAP-positive astrocytes. Our findings suggest that alpha7nAChR malfunction might precede Abeta and tau pathology, offering a different perspective to interpret the failure of anti-Abeta therapies against AD and to find novel therapeutical approaches aimed at restoring alpha7nAChRs-mediated Abeta function at the synapse. |
