Anti-PSEN2 monoclonal antibody, clone BQT 37

Introduction. Alzheimer's disease (AD) is the most frequent degenerative dementia among the elderly population. Families that have an autosomal dominant pattern for AD constitute about 13% of early cases (5 65 years) and less than 0.01% of the total number of patients. Development. Molecular analysis of families with early onset AD has made it possible to identify mutations in three different genes that are responsible for the disease: the gene encoding for the amyloid precursor protein peptide (APP), and the presenilin 1 (PSEN 1) and presenilin 2 (PSEN2) genes. Yet, these genes are involved in less than 5% of the total number of cases of AD. The remaining AD patients are mostly cases of late or familial onset, where the disease appears as a result of a complex interaction among environmental factors and individual predisposing genetic traits. A large number of molecular genetics studies have clearly implicated the APOE epsilon 4 allele as a proven risk factor for the late form of AD in almost all the populations that have been studied. Conclusions. Although the APOE epsilon 4 allele is the only proven genetic risk factor for the late form of the disease, genetic epidemiological studies suggest that other loci are also involved.

Although mutations in three genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), have been identified as genetic causes of early-onset Alzheimer's disease (EGAD), there has been a single report on a PSEN1 mutation in Koreans. In the present study, we performed a genetic analysis of six Korean patients with EGAD. Direct sequencing analysis of the APP, PSEN1 and PSEN2 genes revealed two different mutations of the PSEN1 gene (G206S and M233T) and one mutation of the APP gene (V715M) in three patients with age-at-onset of 34, 35, and 42 yr, respectively. In addition, two patients with age-at-onset of 55 and 62 yr, respectively, were homozygous for APOE epsilon 4 allele. One woman had no genetic alterations. These findings suggest that PSEN1 and APP gene mutations may not be uncommon in Korean patients with EGAD and that genetic analysis should be provided to EGAD patients not only for the identification of their genetic causes but also for the appropriate genetic counseling.