title: Association between cell-bound blood amyloid-β(1-40) levels and hippocampus volume.
abstract: BACKGROUND
  The identification of early, preferably presymptomatic, biomarkers and true etiologic factors for Alzheimer's disease (AD) is the first step toward establishing effective primary and secondary prevention programs. Consequently, the search for a relatively inexpensive and harmless biomarker for AD continues. Despite intensive research worldwide, to date there is no definitive plasma or blood biomarker indicating high or low risk of conversion to AD.
  
  
  METHODS
  Magnetic resonance imaging and β-amyloid (Aβ) levels in three blood compartments (diluted in plasma, undiluted in plasma and cell-bound) were measured in 96 subjects (33 with mild cognitive impairment, 14 with AD and 49 healthy controls). Pearson correlations were completed between 113 regions of interest (ROIs) (45 subcortical and 68 cortical) and Aβ levels. Pearson correlation analyses adjusted for the covariates age, sex, apolipoprotein E (ApoE), education and creatinine levels showed neuroimaging ROIs were associated with Aβ levels. Two statistical methods were applied to study the major relationships identified: (1) Pearson correlation with phenotype added as a covariate and (2) a meta-analysis stratified by phenotype. Neuroimaging data and plasma Aβ measurements were taken from 630 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects to be compared with our results.
  
  
  RESULTS
  The left hippocampus was the brain region most correlated with Aβ(1-40) bound to blood cell pellets (partial correlation (pcor) = -0.37, P = 0.0007) after adjustment for the covariates age, gender and education, ApoE and creatinine levels. The correlation remained almost the same (pcor = -0.35, P = 0.002) if phenotype is also added as a covariate. The association between both measurements was independent of cognitive status. The left hemisphere entorhinal cortex also correlated with Aβ(1-40) cell-bound fraction. AB128 and ADNI plasma Aβ measurements were not related to any brain morphometric measurement.
  
  
  CONCLUSIONS
  Association of cell-bound Aβ(1-40) in blood with left hippocampal volume was much stronger than previously observed in Aβ plasma fractions. If confirmed, this observation will require careful interpretation and must be taken into account for blood amyloid-based biomarker development.
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Sotolongo-Grau
authors.affiliation: Araclon Biotech Ltd, Via Hispanidad 21, Zaragoza, 50009, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Pesini
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain ; Department of Psychiatry, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona, 08035, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Valero
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Lafuente
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Buendía
authors.affiliation: Araclon Biotech Ltd, Via Hispanidad 21, Zaragoza, 50009, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pérez-Grijalba
authors.affiliation: Araclon Biotech Ltd, Via Hispanidad 21, Zaragoza, 50009, Spain.
authors.forename: Itziar San
authors.initials: IS
authors.lastname: José
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ibarria
authors.affiliation: Department of Diagnostic Imaging, Clínica Corachan, Buïgas, 19, Barcelona, 08017, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Tejero
authors.affiliation: Department of Diagnostic Imaging, Clínica Corachan, Buïgas, 19, Barcelona, 08017, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Giménez
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Tárraga
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE Memory Clinic, Institut Català de Neurociències Aplicades, Marquès de Sentmenat, 57, Barcelona, 08029, Spain.
authors.forename: Mercé
authors.initials: M
authors.lastname: Boada
authors.affiliation: Araclon Biotech Ltd, Via Hispanidad 21, Zaragoza, 50009, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sarasa