Carbon 11–Labeled Pittsburgh Compound B Positron Emission Tomographic Amyloid Imaging in Patients With APP Locus Duplication

Abstract

To investigate amyloid accumulation by carbon 11-labeled Pittsburgh Compound B (11 C-PiB) in hereditary cerebral amyloid angiopathy and APP locus duplication. Design, Setting, and Patients: Positron emission tomography with 11 C-PiB and magnetic resonance imaging were performed for 2 patients, 49-year-old and 60-yearold siblings with APP locus duplication, with hereditary Alzheimer disease and cerebral amyloid angiopathy. Main Outcome Measure: Change in 11 C-PiB uptake. Results: Uptake of 11 C-PiB was increased especially in the striatum (caudate nucleus to 225% and 280% of the control mean and putamen to 166% and 185% of the control mean) and in the posterior cingulate (to 168% and 198% of the control mean), and it was marginally increased in other cortical brain areas. The pattern of increased 11 C-PiB uptake was different from that seen in sporadic Alzheimer disease. Conclusions: Amyloid imaging with 11 C-PiB positron emission tomography is a useful tool for detecting in vivo amyloid accumulation in patients with hereditary cerebral amyloid angiopathy. However, the pattern of 11 C-PiB accumulation differs between patients with typical AD and patients with APP locus duplication.

Conversion of amyloid positive and negative MCI to AD over 3 years

“…1 One way to investigate the pathologic changes present in the earliest phase of AD is to study familial AD mutation carriers. Recently, 11 C-PIB PET studies have been performed in such patients and interestingly point mutations 30 and deletions 31 in both symptomatic and asymptomatic carriers of the presenilin-1 gene and duplication of the amyloid precursor protein locus 32 have all been shown to lead to increases in 11 C-PIB uptake, which are predominantly striatal-a pattern distinct from that seen in sporadic AD. Follow-up studies will reveal how the pattern of 11 C-PIB uptake will evolve with the development and progression of clinical symptoms.…”

Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer’s

“…PiB-PET studies showed that Aβ load was highest in the striatum of presymptomatic individuals carrying autosomal dominant mutations in the presenilin 1 and amyloid precursor protein genes (20,21). The present study shows that Aβ deposition is more prominent in the cortical than in the subcortical regions in NL FH+ individuals at risk for LOAD.…”

Target-Specific PET Probes for Neurodegenerative Disorders Related to Dementia

“…An early high PIB retention in the striatum was reported in presymptomatic carriers of presenilin-1 mutation (132). Similarly, an increased PIB uptake also in the striatum and posterior cingulate was observed in patients with amyloid precursor protein locus duplication and cerebral amyloid angiopathy (133). Compared with a sporadic-AD patient, a familial-AD patient who carried His163Tyr mutation in the presenilin-1 gene showed high PIB retention in the striatum but also in the posterior cingulate cortex and the thalamus (39).…”