Involvement of clathrin light chains in the pathology of Alzheimer's disease

Clathrin, which constitutes coated vesicles, plays important roles in neuronal functions. In the brains of the patients with Alzheimer's disease, distribution of clathrin was immunohistochemically investigated using four monoclonal antibodies against clathrin light chains, LCB.1, LCB.2, X-16 and CON.1, to study the involvement of clathrin in the pathology of Alzheimer's disease. LCB.1, LCB.2, X-16, and CON.1 bind to the aminoterminus of the clathrin light chain b(LCb), to the neuron-specific insert of LCb, to the light chain a(LCa), and to LCa and LCb, respectively. In Alzheimer brains, granular staining of LCB.2 around neurons in the hippocampus was weaker or patchily defected in comparison with control brains. Some neurofibrillary tangles and neurons were intensely stained in Alzheimer brains by LCB.2, whereas neurons were weakly stained in control brains. Crowns of some senile plaques in the brains of early onset Alzheimer's disease were positively stained by LCB.2. LCB.1 supported the observations of LCB.2. Reactive astrocytes in Alzheimer brains were intensely stained by X-16. On the other hand, Western blot analysis using LCB.2 and X-16 demonstrated no apparent differences in protein amounts and molecular weights of LCa and LCb between control and Alzheimer brains. These observations demonstrated abnormal distribution of clathrin in Alzheimer brains, implying impairment of axonal transport in this disease.