Loss of α7 Nicotinic Receptors Enhances β-Amyloid Oligomer Accumulation, Exacerbating Early-Stage Cognitive Decline and Septohippocampal Pathology in a Mouse Model of Alzheimer's Disease

摘要: Early Alzheimer's disease (AD) is marked by cholinergic hypofunction, neuronal marker loss, and decreased nicotinic acetylcholine receptor (nAChR) density from the cortex hippocampus. alpha7 nAChRs expressed on projection neurons target regions have been implicated in neuroprotection against beta-amyloid (Abeta) toxicity maintenance of septohippocampal phenotype. We tested role that perform etiology early AD genetically deleting nAChR subunit Tg2576 mouse model for assessing animals cognitive function integrity. Thus, mice transgenic mutant human amyloid precursor protein (APP) were crossed with knock-out (A7KO) to render an animal elevated Abeta absence (A7KO-APP). found learning memory deficits seen 5-month-old APP are more severe A7KO-APP animals. Analyses early-stage preplaque decline revealed signs neurodegeneration hippocampus as well loss functionality basal forebrain These changes occurred concomitant appearance a dodecameric oligomer was absent all other genotypic groups, generating hypothesis increased soluble oligomeric may underlie additional impairment function. appear serve neuroprotective through phenotype preservation hippocampal integrity possibly influences accumulation oligomerization.