title: Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B.
abstract: Down syndrome (DS) is one of the most common causes of intellectual disability. Although DS accounts for only 15% of all individuals with intellectual disabilities, adults with DS account for approximately 60% of individuals with intellectual disabilities and Alzheimer's disease. This is thought to be because of overproduction of the β-amyloid (Aβ) protein due to trisomy for the Aβ precursor protein gene on chromosome 21. Pittsburgh compound B (PiB) is a noninvasive in vivo positron emission tomography tracer used to image amyloid deposition in living humans. Studies using PiB have shown an age-dependent asymptomatic amyloid deposition in more than 20% of the cognitively normal elderly population. Presymptomatic carriers of presenilin (PS-1) and Aβ precursor protein gene mutations who are destined to develop Alzheimer's disease also show preclinical amyloid deposition. This report describes a pilot study involving the use of PiB in seven adults with DS (age: 20-44 years). Compared with objective cutoffs for amyloid positivity in older non-DS cognitively normal control subjects, only two of the seven DS subjects (age: 38 and 44 years) showed increased PiB retention. The remaining five subjects aged between 20 and 35 years showed no detectable increase in PiB retention. Interestingly, the two subjects who showed elevated PiB retention showed a striatal-predominant pattern similar to that previously reported for PS-1 mutation carriers. These results demonstrate the feasibility of conducting PiB positron emission tomography scanning in this special population, and suggest a link between Aβ overproduction and early striatal deposition of fibrillar Aβ.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Handenbl@upmc.edu
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Handen
authors.forename: Ann D
authors.initials: AD
authors.lastname: Cohen
authors.forename: Umapathy
authors.initials: U
authors.lastname: Channamalappa
authors.forename: Peter
authors.initials: P
authors.lastname: Bulova
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Cannon
authors.forename: William I
authors.initials: WI
authors.lastname: Cohen
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
mesh_terms: D000328:Adult; D058227:Amyloidogenic Proteins / Q000032:analysis*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging*; D004314:Down Syndrome / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008297:Male; D059906:Neuroimaging / Q000379:methods; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles; D055815:Young Adult
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D058227:Amyloidogenic Proteins; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013844:Thiazoles