P4‐008: APP INTRON 7 POLYMORPHISM AND PLASMA AMYLOID‐BETA PEPTIDE LEVELS CAN PREDICT THE ONSET OF DEMENTIA IN DOWN's SYNDROME

• DOI: 10.1016/j.jalz.2014.05.1522
• Publication Date: 2014-09-06T15:14:45Z
• Authors: Alyma A. Somani; Emma Jones; Jill Rasmussen; Clive G. Ballard
• Keywords: Pathogenesis; Amyloid beta; Amyloid (mycology)

Deposition of the beta-amyloid peptide is thought to be an important initial step in progression and pathogenesis Alzheimer's disease. Amyloid beta peptides Ab1-40 Ab1-42, two major species beta-amyloid, are generated by sequential proteolytic cleavage amyloid precursor protein (APP). Studies suggest that Ab1-42 deposition essential AD which aggregates rapidly resulting plaque formation than Ab1-40. Individuals with Down's syndrome (DS) have increased levels risk AD. suggested increase dementia DS may mediated precedes appearance Plasma both been demonstrated but a relationship yet established. However, tetranucleotide repeat, attt 5-8, intron 7 APP has shown alter age onset DS. We compared plasma amyloid-beta at baseline 12 months 166 demented non-demented adults were measured examination (baseline) month follow up. assessed for cognitive functional outcome intervals. Following genotyping 7, we examined link between 5-8 polymorphism developing before 45. Compared patients, patients significantly 34% (p=0.03) In contrast, mean lower 52% without counterparts dementia. Data indicated striking association 3 copies 6 allele earlier DS; people developed years earlier. These results support hypothesis play role determining associated addition, confirm significant impact on Along over expression seen DS, splice variants gene forming isoforms not only production, also abnormal tau isoforms. Hence, further investigation necessary determine production its