THYROID EPITHELIAL-CELLS PRODUCE LARGE AMOUNTS OF THE ALZHEIMER BETA-AMYLOID PRECURSOR PROTEIN (APP) AND GENERATE POTENTIALLY AMYLOIDOGENICAPP FRAGMENTS

The Alzheimer beta-amyloid precursor protein (APP) is a transmembrane glycoprotein from which the amyloid beta-protein is proteolytically de rived. The latter is a hydrophobic peptide that can aggregate and form s the core of the senile plaques found in the brains of patients suffe ring from Alzheimer's disease (AD). In view of the known association b etween familial AD and thyroid autoimmune disease, the expression patt ern and cellular processing of APP in human thyroid cells were investi gated. Cultured thyroid epithelial cells and homogenized thyroid tissu e from normal and pathological thyroid samples were analyzed by immuno blotting using specific N- and C-terminal APP antibodies as well as by reverse transcription-polymerase chain reaction in which two sets of oligonucleotide primers were used. The results of these studies demons trated that APP isoforms 770 and 751 were expressed in fresh thyroid e xtracts as well as in cultured thyroid epithelial cells, with APP 770 being the predominant form. Compared to other types of cells, such as lymphocytes and fibroblasts, thyroid epithelial cells produced larger amounts of APP. Most of the mature protein was cleaved within the amyl oid beta region, as a result of which a large N-terminal APP fragment was released into the culture medium, whereas a C-terminal nonamyloido genic fragment of 14 kilodaltons (kDa) was retained within the cell. I nterestingly, thyroid epithelial cells also contained larger C-termina l APP fragments of 21, 35, and 41 kDa. From the sizes of these fragmen ts it could be deduced that they contained the entire amyloid beta seq uence and were thus potentially amyloidogenic. The 41-kDa fragment was unique to thyroid cells. These fragments may be released into the cir culation after thyroid cell damage. Increased/altered thyroid APP expr ession in familiar AD may induce alterations in thyroid epithelial cel ls and cell damage, and thus explain the frequent occurrence of thyroi d autoimmunity in this disease.