The multifactorial causes impacting the risk of developing sporadic forms of 
Alzheimer's disease (AD) remain to date poorly understood. Epidemiologic studies 
in humans and research in rodents have suggested that hypothyroidism could 
participate in the etiology of AD. Recently, we reported that adult-onset 
hypothyroidism in rats favors β-amyloid peptide production in the hippocampus. 
Here, using the same hypothyroidism model with the antithyroid molecule 
propythiouracyl (PTU), we further explored AD-related features, dysfunctional 
cell-signaling mechanisms and hippocampal-dependent learning and memory. In vivo 
MRI revealed a progressive decrease in cerebral volume of PTU-treated rats. In 
the hippocampus, hypothyroidism resulted in tau hyperphosphorylation and 
increases in several proinflammatory cytokines. These modifications were 
associated with impaired spatial memory and reduced hippocampal expression of 
signaling molecules important for synaptic plasticity and memory, including 
neurogranin, CaMKII, ERK, GSK3β, CREB, and expression of the transcription 
factor EGR1/Zif268. These data strengthen the idea that hypothyroidism 
represents an important factor influencing the risk of developing sporadic forms 
of AD.