Lithostathine and pancreatitis-associated protein are involved in the veryearly stages of Alzheimer's disease

According to one of the theories formulated to explain the etiology of Alzh eimer's disease (AD), amylosis may reflect a specific inflammatory response . Two inflammatory proteins, lithostathine and PAP, were evidenced by immun ohistochemistry in senile plaques and neurofibrillary tangles of patients w ith AD. In addition, lithostathine and PAP were significantly increased in the cerebrospinal fluid of patients with AD when compared to patients with multiple sclerosis, another inflammatory disease, and to normal control sub jects. However, no correlation was observed with age of occurrence. Further more, lithostathine and PAP were increased even at the very early stages of AD, and their level remained elevated during the course of the AD unlike T NF alpha whose level, very high at very early stages, regularly decreased. Finally, if part of lithostathine and PAP are synthesized in the brain, a l arge part comes from serum by passage over the blood-brain barrier. These r esults indicate (i) the existence of an acute phase response followed by a chronic inflammation in AD, and (ii) that lithostathine and PAP are involve d even at the first pre-clinical biochemical events of AD. In addition, bec ause lithostathine undergoes an autolytic cleavage leading to its precipita tion and the formation of fibrils, we believe that it may be involved in am yloidosis and tangles by allowing heterogeneous precipitation of other prot eins. (C) 2001 Elsevier Science Inc. All rights reserved.