Abstract
Down syndrome (DS) is accompanied by cognitive manifestations resulting from full or partial extra chromosome 21. Amyloid precursor protein overexpression and the exponential aggregation of amyloid beta in the brain cause dementia in individuals with DS. This study aimed to uncover early serum marker candidates of amyloid precursor protein-like protein 1 beta species denoted APL1β25, APL1β27 and APL1β28 and the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) as predictors of Alzheimer's disease (AD) in adolescents with DS and to elucidate the correlation between these parameters and the cognition of DS patients. This study included 30 DS cases (13-18 years old) with full trisomy 21 in addition to 30 healthy age-matched controls. The cognitive decline in DS subjects was evaluated using the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (Short IQCODE). Serum levels of APL1b25, ALP1b27, ALP1b28 and MHPG were evaluated using enzyme-linked immunosorbent assay. The results indicated a significant positive correlation (P = 0.045) between IQCODE short score and APL1b25 serum level in DS patients. Also the present data recorded a significant reduction (P < 0.05) in APL1b25, APL1b27, APL1b28 and MHPG serum levels in DS patients contrary to the controls. Our findings confirm the impaired metabolism of APL1 peptides and the degeneration of noradrenergic neurons in DS patients which ultimately leads to early onset of AD. Noteworthy, the serum level of APL1b25 could be a prospective blood-based marker for early detection of cognitive decline and AD in adolescents with DS.