title: Alzheimer's disease: are blood and brain markers related? A systematic review.
abstract: Peripheral protein biomarkers of Alzheimer's disease (AD) may help identify novel treatment avenues by allowing early diagnosis, recruitment to clinical trials, and treatment initiation. The purpose of this review was to determine which proteins have been found to be differentially expressed in the AD brain and whether these proteins are also found within the blood of AD patients.
  
  
  
  A two-stage approach was conducted. The first stage involved conducting a systematic search to identify discovery-based brain proteomic studies of AD. The second stage involved comparing whether proteins found to be differentially expressed in AD brain were also differentially expressed in the blood.
  
  
  
  Across 11 discovery based brain proteomic studies 371 proteins were at different levels in the AD brain. Nine proteins were frequently found, defined as appearing in at least three separate studies. Of these proteins heat-shock cognate 71 kDa, ubiquitin carboxyl-terminal hydrolase isozyme L1, and 2',3'-cyclic nucleotide 3' phosphodiesterase alone were found to share a consistent direction of change, being consistently upregulated in studies they appeared in. Eighteen proteins seen as being differentially expressed within the AD brain were present in blood proteomic studies of AD. Only complement C4a was seen multiple times within both the blood and brain proteomic studies.
  
  
  
  We report a number of proteins appearing in both the blood and brain of AD patients. Of these proteins, C4a may be a good candidate for further follow-up in large-scale replication efforts.
authors.affiliation: GKT School of Medical Education King's College London London United Kingdom.
authors.forename: Ali T
authors.initials: AT
authors.lastname: Khan
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology and Neuroscience King's College London London United Kingdom; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia London United Kingdom.
authors.forename: Richard J B
authors.initials: RJ
authors.lastname: Dobson
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology and Neuroscience King's College London London United Kingdom; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia London United Kingdom.
authors.forename: Martina
authors.initials: M
authors.lastname: Sattlecker
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology and Neuroscience King's College London London United Kingdom; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia London United Kingdom.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kiddle