Pittsburgh Compound-B and Alzheimer’s Disease Biomarkers in CSF, Plasma and Urine: An Exploratory Study

Abstract

Background: The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring β-amyloid (Aβ) load. Associations between PET PIB and cerebrospinal fluid (CSF) Aβ1–42 and apolipoprotein E Ε4 (APOE Ε4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer’s disease (AD) are less investigated. Method: PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD. Results: PIB retention was constant over 1 year, inversely related to low CSF Aβ1–42 (p = 0.01) and correlated positively to the numbers of the APOE Ε4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = –0.59, p = 0.07), and plasma cystatin C (r = –0.56, p = 0.09). Conclusion: PIB retention is strongly related to CSF Aβ1–42, and to the numbers of the APOE Ε4 allele.

Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study

“…Among the studies that have thus far examined the association between amyloid PET and CSF amyloid-β 42 (Fagan et al , 2006, 2007, 2009 b ; Forsberg et al , 2008, 2010; Jagust et al , 2009; Tolboom et al , 2009; Degerman Gunnarsson et al , 2010; Weigand et al , 2011; Landau et al , 2013; Zwan et al , 2014, 2016; Palmqvist et al , 2014, 2016; Mattsson et al , 2015), few have directly compared tau levels in those with concordant and discordant biomarker results. In the studies that have, tau was found to be higher in PET+/CSF+ subjects, relative to those PET−/CSF+ (Palmqvist et al , 2016; Zwan et al , 2016), in PET+/CSF+ subjects, relative to those PET−/CSF+ (Mattsson et al , 2015; Zwan et al , 2016), and in subjects discordant with PET positivity, relative to both those concordant negative and discordant with abnormal CSF (Zwan et al , 2016).…”

“…This inverse relationship has been confirmed by many groups across cognitively normal, mild cognitive impairment (MCI) and Alzheimer’s disease subjects, leading to the view that these biomarkers are interchangeable in defining ‘amyloid-positivity’ (Fagan, 2015). Though this inverse relationship has generally been observed between both measures, a subset of cases shows discordant results, with either abnormal CSF amyloid-β 42 but normal amyloid PET, or normal CSF amyloid-β 42 but abnormal amyloid PET (Forsberg et al , 2008; Jagust et al , 2009; Degerman Gunnarsson et al , 2010; Landau et al , 2013; Palmqvist et al , 2014; Zwan et al , 2014; Mattsson et al , 2015). While discordance in most cases is due to abnormal CSF amyloid-β 42 in subjects with normal amyloid PET, isolated PET positivity has been reported in both MCI and Alzheimer’s disease (Koivunen et al , 2008; Forsberg et al , 2010; Landau et al , 2013; Zwan et al , 2014; Leuzy et al , 2015; Mattsson et al , 2015; Palmqvist et al , 2016).…”

Comparison of Immunosorbent Assays for the Quantification of Biomarkers for Alzheimer’s Disease in Human Cerebrospinal Fluid

“…The clinical diagnosis of AD today is mainly based on the results of different neuropsychometric tests [1], laboratory tests [2,3], the patient’s history and clinical examinations. Recently, also brain imaging is emerging as a new tool in the diagnosis of AD [4,5]. Reliable biomarker tests could indicate the development of neurodegeneration in early stages of AD and may be a prerequisite for disease-modifying therapies like vaccination strategies which are currently under investigation [6].…”

Impact of Beta-Amyloid-Specific Florbetaben PET Imaging on Confidence in Early Diagnosis of Alzheimer’s Disease

“…A pivotal problem in early diagnosis of AD is that clinical symptoms as assessed by neuropsychological tests become apparent only after massive neuronal cell loss has already taken place. Today, there is general agreement that diagnosis of AD should be based on the results of various neuropsychological tests [1], brain imaging [2][3][4], cerebrospinal fluid (CSF) and blood studies [5][6][7], C.G.S. and O.P.…”