A group of pancreatic islet β cell‐like neurons are vulnerable to energy deficiency

Background Alzheimer’s disease (AD) bear resemblance to the diabetes mellitus for that both of them exhibit beta‐amyloid (Aβ) deposition, insulin resistance and glycometabolic disorder. Peripheral islet β cells produce insulin and islet amyloid peptides, but whether there is a group of neurons in the brain like islet β cells is not clear. Method Hybridize APP/PS1 transgenic mice and CaMKII‐CreERT2/+ ;Tpkfl/fl strain, with tamoxifen induced Tpk knockout at 6 months of age, to form a model of energy deficiency. Labeling neuron and microglia with NeuN and Iba1 antibody, and immunofluorescence was used to observe Aβ, insulin‐like growth factor expression. TUNEL staining was applied to test cell apoptosis. Result We found that layer 5 cortical pyramidal neurons are strongly marked by Aβ antibody, 4G8, in APP/PS1 transgenic mice. Immunofluorescence showed that these 4G8‐positive neurons colocalized with insulin‐like growth factor 1/2 and highly expressed prohormone convertase 2. Further, we conditionally knocked out Tpk gene, a key gene involved in glucose metabolism, in excitatory neurons of APP/PS1 mice. Over time, NeuN and Iba1 labeling showed that the significant loss of neuron and activation of microglia happened in layer 5 cerebral cortex at the earliest. Additionally, the 4G8‐positive neurons in this layer were stained by TUNEL and markedly reduced in the early stage. Conclusion We found a group of islet β cell‐like neurons that are vulnerable to glucose energy impairment, suggesting a group of vulnerable neurons in sporadic AD, and implicating the cytological mechanism of association between AD and diabetes.